8 September 2025

GENERAL INFORMATION GUIDELINE

This guideline is intended to provide recommendations to applicants wishing to submit applications for the registration
of medicines. It represents the South African Health Products Regulatory Authority’s (SAHPRA)’s current thinking on the
safety, quality and efficacy of medicines. It is not intended as an exclusive approach. SAHPRA reserves the right to request
any additional information to establish the safety, quality, and efficacy of a medicine, in keeping with the current
knowledge at the time of evaluation. Alternative approaches may be used but these should be scientifically and technically
justified. SAHPRA is committed to ensuring that all registered medicines will be of the required quality, safety and
efficacy. It is essential that applicants comply with the administrative requirements to prevent delays in the processing
and evaluation of their applications. This guideline is relevant only to human medicines, including biological and
complementary medicines. Separate guidelines apply to the registration of veterinary medicines, medical devices and
other health products.

Guidelines and application forms are available from the website: www.sahpra.org.za.

Document History
Final Reason for Amendment Effective Date
Version
1 First publication released for implementation and comment May 2003

1 Date for finalisation/implementation Dec 2003

2 General editing – page numbers in index, 2.5, 3.1.2, 3.1.3 a) b), 4.1, 4.4, 4.17, 8, 12 July 2006
10, and amendment of sections 2.2.2, 2.9, 3.1.4, 4.2, 4.5, 4.6, 4.7, 4.14, 5, 5.2,
13.1, 13.2, 13,3, 13.4, 13.5, 13.6, 13.7, Attachment A
3 Additions to 2.7.5, 2.10.5, 13.4; amendments to 4, 5.2, Attachment A 25 June 2007

4 Amendment of sections 2.9, 2.10.5, 3.1.3 a), 4, 4.7, 4.10, 5.1, 01 August 2008
5.2, 13.3, 13.4, Attachment A
5 Removal of section 12 “Standardised package insert warnings” and inclusion in March 2010
the new “Package Insert Standardised Texts” guideline
Removal of Attachment B re: package insert information
Amendment to section 4.9
6 Inclusion of references to the ZA CTD – sections 2.11, 3, 4, 4.14, 5, 13.1
Amendment of section 2.5
Amendment, for clarity, of sections 2.10.5 k), 3.1.2, 3.1.3 c), 3.1.4, 3.4, 3.5, 4.3, 21 June 2010
4.5, new 4.6, 4.9 (original 4.8), 4.10 (original 4.9), 4.17, 5.2, 5.4, 13.3, 13.9 & new
section 3.1.1 p)

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7 Amendment of name of “Post-registration Amendments”, “Guidance for

submission of SA CTD / eCTD Module 1" guidelines, and administrative
amendments:
Sections 2.5, 3, 3.1.1o), 4, 4.5, 5, 5.2.6, 5.2.8, 5.4, 13, 13.1, 13.2, Attachment A;
new 4.11 and renumbered.
Amendment of 2.2.2 for clarification & in line with CTD guideline.
Clarification of 4.3 & 4.4 in accordance with Biostudies guideline March 2011
3.9 & 4.4 and insertion of 4.11 in accordance with Quality and Bioequivalence
Guideline 2.1.2.11.
Deletion of “independent” in 6.2 & 8.1.
Insertion of “(including batch specific)” for shelf-life extension under working
code VSE in accordance with the Amendments guideline, Type C Inspectorate
category 19.
7 13.1 Correction
June 2011

8 Deletion of Section 9 on Proprietary Names, Attachment A (pre-screening

checklist) August 2012
Amendment of 2.11, 3.1.4, 4, 4.2, 5.2.8, 6, 13.2, 13.9
9 Transition from MCC to SAHPRA
May 2019
To include sections that have been changed or deleted
10 Updated to align with new processes and guidelines July 2019

11 New template and numbering April 2023

Updated to align with new processes and guidelines
Amended sections: 1.2; 3.1; 3.4; 3.6; 3.7; 3.9; 3.14; 3.15; 4; 5; 6; 7; 9; 10
Added sections: 2.5; 3.5; 3.13; 3.16; 3.17; 3.18; 3.19
Deleted information on coding of submissions
Deleted reliance information in section 3.8
Deleted sections 3,10; 3,11 & 3,12
12 Amended section 3.15 to include the number of review times and response
timelines.
Deleted section 3.9 – SAHPRA Recognised Regulatory Authorities since it is
December 2023
included in the Reliance Guideline.
Amended 3.12 to include email addresses.
Amended section 8 to include the guideline number.
13 Updated to align with new processes and guidelines October 2025

DR BOITUMELO SEMETE-MAKOKOTLELA
CHIEF EXECUTIVE OFFICER

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Contents
Document History ........................................................................................................................................... 1
Glossary .......................................................................................................................................................... 5
1. INTRODUCTION ......................................................................................................................................... 7
1.1Purpose ………………………………………………………………………………………………………………………………………………..7

1.2Scope ......................................................................................................................................................... 7
2. LEGAL PROVISION ...................................................................................................................................... 7
3. GENERAL .................................................................................................................................................... 8
3.1Applicant/PHCR/HCR ................................................................................................................................. 8
3.2Confidentiality/Secrecy ............................................................................................................................. 8
3.3 Language ………………………………………………………………………………………………………………………………………..9

3.4 eCTD Identifier/Application Number……………………………………………………………………………………………….9

3.5 Where to submit applications …………………………………………………………………………………………………………9

3.6 When a product should be registered ……………………………………………………………………………………………9

3.7 Types of applications ……………………………………………………………………………………………………………………10

3.8 Evaluation Pathways …………………………………………………………………………………………………………………… 11

3.9 SAHPRA's Recognised Regulatory Authorities ………………………………………………………………………………12

3.10 Expedited review process …………………………………………………………………………………………………………… 12

3.11 Medicines for Use in a Public Health Emergency (PHE) ………………………………………………………………..12

3.12 Fees …………………………………………………………………………………………………………………………………………… 12

3.13 Same or separate applications ……………………………………………………………………………………………………..12

3.14 Unregistered old medicines…………………………………………………………………………………………………………..14

3.15 Clones and Replicas……………………………………………………………………………………………………………………….15

3.16 Variations Permitted during the Registration process ………………………………………………………………. 16

3.17 Permissible review response rounds and period for response submissions ………………………………….16

3.18 Classification of queries…………………………………………………………………………………………………………………17

3.19 Renewals ……………………………………………………………………………………………………………………………………18

3.20 Cancellation or Withdrawal of applications ………………………………………………………………………………….18

4. REQUIREMENTS OF AN APPLICATION …………………………………………………………………………………………..18

5. PROPRIETARY NAME AND SCHEDULING OF SUBSTANCE AND MEDICINE ……………………………………..19

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6. MANUFACTURING REQUIREMENTS …………………………………………………………………………………………….19

7. SAMPLES ……………………………………………………………………………………………………………………………………...19

8. STANDARD PROFESSIONAL INFORMATION WARNINGS AND INFORMATION ……………………………… 19

9. RESPONSIBILITIES OF EACH UNIT ………………………………………………………………………………………………… 20

9.1 PEM (Sub-Programme 4) ……………………………………………………………………………………………………………… 20

9.2 IRC (Programme 3) ……………………………………………………………………………………………………………………….21

9.3 CEM (Sub-Programme 4) ……………………………………………………………………………………………………………. .21

9.4 HPA (Programme 2) …………………………………………………………………………………………………………………… 21

10. REFERENCES ……………………………………………………………………………………………………………………………… …21

11.VALIDITY .................................................................................................................................................. 22

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Glossary
Abbreviation/ Term Meaning

API Active Pharmaceutical Ingredient (also known as Drug Substance)

Applicant Organisation creating and submitting the eCTD submission. Can refer to either
the PHCR or HCR
Application number A unique identifier for a product application. Each product (clones, duplicates,
strengths) will have a unique application number.
The Application Number will remain with the product for its full life cycle and
in archiving, even if it is transferred to a new applicant.
The new SAHPRA Portal will automatically issue the Application Number.
Application ID A unique identifier for an eCTD application. An Application ID must be issued
before an eCTD submission can be submitted using version 3.1 (or higher)
specifications.
The same Application ID will be used for all Sequences of an eCTD Application
and cannot ever be changed.
The Application ID will also be used as the directory name in the top-level
directory. Note for legacy applications, the top-level directory name should
continue to be the eCTD identifier used in earlier sequences.

CD Compact Disc
CD-ROM Compact Disc Read-Only Memory
CEM Clinical Evaluation and Management
Clone Application submitted by the innovator of an already registered NCE, as a
copy of its own product under a different proprietary name and application
number as a follow-up sequence of the original registered (Master) product,
as part of the life cycle of the Master Application. The Application ID is the
same as the Master’s.
CTD Common Technical Document as defined by ICH and SAHPRA. Modules 2-5
are based on the ICH internationally accepted structure for Quality,
Nonclinical and Clinical Information. SAHPRA defines module 1 and sections
2.3.R / 3.2.R Regional Information.
Dossier A collection of electronic documents provided over a period. The Application
refers to the entire life cycle of a registration filed under an Application ID.
Duplicate A duplicate application may be for an innovator, a generic, or a biosimilar
product and is defined as two or more applications submitted simultaneously
by the same applicant that are identical in every aspect except for the
proposed proprietary name(s). A duplicate application must be submitted at
the same time as the master application.
eCTD Electronic Common Technical Document – an international electronic
standard for the Common Technical Document (CTD) providing the means for
transferring information from Applicants to Authorities.
eCTD application A collection of electronic documents compiled by an applicant/PHCR in
compliance with South African legislation and guidelines to seek registration
of a medicine, or any amendments thereof.

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An eCTD Application is also referred to as an application.

eCTD Submission A collection of Sequences covering a specific request, which includes the first
sequence of the activity and any follow-up Sequences, for example,
supplemental information, responses to recommendations, withdrawals, etc.

FPP Finished Pharmaceutical Product

HCR Holder of Certificate of Registration
HPA Health Products Authorisation
ICH International Council for Harmonisation (of Technical Requirements for
Registration of Pharmaceuticals for Human Use)
INN International Non-proprietary Name
IRC Inspectorate and Regulatory Compliance
Line Extension A line extension application is an application for registration from the same
applicant, where, for instance, the pharmaceutical form and/or strength
differs from one or more other pharmaceutical products for which the
applicant already holds a registration certificate.
PEM Pharmaceutical Evaluation Management
PHCR Proposed Holder of Certificate of Registration
PI Professional Information
PIL Patient Information Leaflet
Q & BE Quality and Bioequivalence
QIS Quality Information Summary
QOS Quality Overall Summary
Replica A replica is defined as a copy of an already registered generic product,
submitted by the same applicant at any stage during the life cycle of the
original registered (Master) product, under a different proprietary name and
application number, as a follow-up sequence to the original registered
(Master) product. Thus, the Application ID is the same as the Master’s.
RRA Recognised Regulatory Authority
SAHPRA South African Health Products Regulatory Authority

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1. INTRODUCTION
The registration of a medicine in South Africa is governed by the provisions and requirements of the
Medicines and Related Substances Act, 1965 (Act No. 101 of 1965), (hereafter 'the Act') and the
regulations and guidelines published in terms thereof.

These guidelines describe the information required for the registration of “medicines” and for an
application to amend a registered medicine. The information submitted will be evaluated in terms of
the provisions of the Act.

Medical devices, including in vitro diagnostics, are addressed in separate guidelines.

It is a legal requirement that data submitted for evaluation substantiate all claims and meet the technical
requirements of quality, safety, and efficacy of the product for the purposes for which it is intended. The
guidelines are meant to guide the applicant in meeting the requirements of the Act. It is acknowledged,
however, that in some instances, scientific developments may dictate alternative approaches. When a
deviation from a guideline is decided upon, a detailed motivation should be included in the expert report
submitted with the application, providing the reason(s) for the deviation and justification for the
alternative approach.

Whenever there is doubt, applicants are advised to consult SAHPRA for confirmation and/or clarification
before completing and submitting the application form; refer to the website for contact details.
Applicants should always refer to the current version of the relevant guidelines and the addenda thereto
before completing the application form.

Guidelines are constantly evolving due to scientific developments and harmonisation of the requirements
of regional and international regulatory authorities. SAHPRA endeavours to regularly update the
guidelines to reflect current thinking and keep its technical requirements and evaluation policies in line
with “best international medicines regulatory practice”.

1.1 Purpose

This guideline aims to assist applicants in the preparation of documentation for the registration of
medicines for human use. The types of medicine include a new medicine for a new chemical entity (NCE),
including clones, a multisource (generic) product, including replicas, a product line extension, a
biological medicine, and a complementary medicine.

1.2 Scope

These guidelines are relevant only to human medicines, including biological and complementary
medicines. Separate guidelines apply to the registration of veterinary medicines (SAHPGL-PEM-VET-04
Guideline for Registration of Veterinary Medicines) and medical devices.

2. LEGAL PROVISION
Legislation requires that SAHPRA shall register every medicine before it may be sold/marketed. An
application for the registration of a medicine should therefore be submitted for evaluation and approval.

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3. GENERAL
3.1 Applicant / PHCR / HCR
The term ‘applicant’ can refer either to the proposed holder of the certificate of registration (PHCR), as
in the case of a new registration, or to the holder of the certificate of registration (HCR), as in the case of
a variation application. Throughout this document, the term ‘applicant’ is used to refer to either the PHCR
or the HCR, based on whichever is applicable in the context.
Eligibility to apply for registration of a medicine is governed by Regulation 16 of the Act. An application
may be made by any of the following:
a) a person, body corporate/juristic person, company, residing and doing business in South Africa.
b) a close corporation incorporated in South Africa; or
c) a company in South Africa with at least
- a responsible delegated person residing in South Africa and
- an authorised person residing in South Africa who must be a person with appropriate
knowledge of all aspects of the medicine and who shall be responsible for
communication with the Authority.
The pharmacist should sign the application submitted authorised to communicate with the Authority.
This pharmacist should be in the full-time employ of the company and may be:
• the Responsible Pharmacist in terms of the Pharmacy Act, 1974 (Act 53 of 1974) as amended, or
• another registered pharmacist responsible for regulatory affairs and with appropriate
knowledge of all aspects of the medicine.
The following should be included:
• proof of current registration (copy of certificate) of the pharmacist who signed the dossier, and
• proof of current registration of the Responsible Pharmacist in terms of Act 53;
• an individualised, person-specific letter of authorisation for the signatory, issued by the person
responsible for the overall management and control of the business (CEO). (Note that a letter is not
required for the Responsible Pharmacist if they sign the application.)
An applicant should submit a Site Master File (SMF) in accordance with the Site Master File Guideline
SAHPGL-INSP-04. For subsequent applications, reference to the allocated SMF number will suffice.

3.2 Confidentiality/Secrecy
The confidentiality of information submitted to SAHPRA is governed by Section 34 of the Act. The
Authority, advisory committee members, or staff of the Authority may NOT:
• disclose to any person, any information acquired in the exercise of powers or performance of functions
under the Act and relating to the business affairs of any person, except
§ for the purpose of exercising his/her powers, or for the performance of his/her functions
under the Act, or
§ when required to do so by any competent court or under any law, or
§ with the written authority of the CEO, or
• use such information for self-gain or for the benefit of his employer.

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SAHPRA may insist on written confirmation of the identity and affiliation of an individual inquiring
telephonically or in person about a medicine. No information shall be disclosed telephonically unless
the Authority staff member knows the enquirer is entitled to receive the information.

If information is received by anyone other than the intended recipient(s), it must not be used for
personal gain, organisational benefit or shared with any third party. The recipient must notify the
sender immediately and delete the information from all systems as soon as possible.

3.3 Language

In terms of Regulation 16 (4) of the Act, all applications and supporting data submitted to SAHPRA should be
presented in English (UK)). An English translation should accompany original documents not in English.

3.4 Application ID and Application Number

Refer to the guideline 2.21 ZA-SAHPRA-eCTD-Specifications-v3.1

3.5 Where to submit applications

The SAHPRA Engagement Portal is an online platform designed to facilitate interactions between
applicants and SAHPRA. The portal enables users to submit and track applications, manage their profiles
and ensure compliance with regulatory requirements. File Transfer Protocol (FTP) details must be set
under the Organisation Details before attempting to create applications that require eCTD uploads to the
SAHPRA FTP Server. A request for the FTP User Guide for Files/Dossier Submission and access to the FTP
should be sent to [email protected]. When requesting access to the FTP, applicants should
include the company name and license number.

3.6 When should a product be registered

A product is liable for registration with SAHPRA if any of the following apply:
i) Any of the ingredients of a product is listed in one of the Schedules for the Act;
ii) The product is a medicine by virtue of the definition of a medicine in the Act.
The Act defines a medicine as:
"any substance or mixture of substances used, or purported to be suitable for use, or
manufactured or sold for use in;
(a) the diagnosis, treatment, mitigation, modification or prevention of disease,
abnormal physical or mental state, or the symptoms thereof in man; or
(b) restoring, correcting, or modifying any somatic or psychic or organic
function in man; and includes any veterinary medicine.”
iii) If the product falls under any of the pharmacological classifications as specified in Annexure 1 and
2 to the Regulations.
iv) The intended use of a product and the text/words used in promoting the product, even if no claims
are reflected on the label, render the product registerable.
The relevant provisions and guidelines shall apply to a medicine called up as a complementary medicine.

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3.7 Types of applications

Medicine applications for registration for humans are divided into the following types for the
determination of fees and allocation to reviewers for evaluation:
New chemical entity applications (including clones) that include non-clinical and clinical information in
support of the efficacy and safety of the formulation/dosage form, indication(s) and dosage regimen.
Multisource/generic applications (including replicas) and extension applications that include:
• clinical information in support of efficacy and safety of the formulation/dosage form, or
indication(s) or dosage regimen.

• comparative bioavailability/bioequivalence studies as proof of efficacy.

• comparative dissolution studies as proof of efficacy.
• any other comparative studies as proof of efficacy.
• others, not mentioned above, for e.g., liquids/solutions.

Category D Medicines: Guideline 7.03 - Use of the ZA-CTD Format in the Preparation of a Registration
Application” should also be followed to determine completeness.

Data provided in applications for registration of Category D medicines should be in the latest version of the
Common Technical Document (ZA-CTD) format as published by SAHPRA. A risk-based approach is
undertaken for Category D medicines where discipline-specific medicines are considered across a range
from HIGH RISK (clinical evidence required in justification of safety and efficacy) to LOW RISK (traditional
evidence may be submitted in justification of safety and efficacy) based primarily on indication but also on
composition and dosage form.

The Authority will, in the future, consider online mechanisms for submitting applications for the registration
of Category D Medicines, which will continue to utilise the CTD format.

The following guidelines are relevant to the compilation of applications for registration of
Complementary Medicines:
• Guideline 7.01 - Discipline-Specific Safety and Efficacy
• Guideline 7.04 - Health Supplements Safety and Efficacy
• Guideline 7.05 - Registration Application ZA-CTD – Quality
• Guideline 7.06 – Specified Substances

Biological medicines: Biopharmaceuticals and Biosimilars

Biological medicine: A medicine where the active ingredient/s and/or key excipients have been derived
from living organisms or tissues or manufactured using a biological process. Biological medicines can be
primarily defined by reference to their method of manufacture (the biological process). These include
inter alia medicines prepared from the following substrates:

• Microbial cultures (fermentation),

• Plant or Animal Cell cultures (including those resulting from recombinant DNA/RNA or
hybridoma techniques,
• Extraction from biological tissues; and

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• Propagation of live agents in embryos or animals.

The living substrate may be genetically modified in several ways to provide the required active ingredient,
including recombinant DNA technology or hybridoma techniques.

Biological Medicines include, but may not be limited to the following:

• Plasma-derived products, e.g., clotting factors, Immunosera,
• Vaccines,
• Biotechnology-derived medicinal products (rDNA products), e.g., rHu-antihemophilic factors,
hormones, cytokines, enzymes, monoclonal antibodies, erythropoietin’s, and
• Human Gene therapy.

It has been the practice, in South Africa, that SAHPRA will decide that certain well-characterised low-
molecular-weight medicinal biological compounds, such as antibiotics, insulin, etc., be excluded from
biological medicine status.

Biopharmaceutical: Patented biological medicine.

Biosimilar: Biological medicines that are manufactured to be similar to the registered originator/ innovator
medicines.

3.8 Evaluation Pathways

Medicines applications for new registrations and variations in South Africa will follow one of four
evaluations/review pathways:

• Full review
• Abridged review
• Verified review
• Priority review

Full review is defined as a comprehensive/thorough review of all aspects of the dossier, based primarily on
the evaluation of data (and summaries thereof) submitted by the applicant. This is the default evaluation
pathway for new registrations and variations not previously approved by SAHPRA or an RRA, where
reliance documentation provided to SAHPRA is deemed to be insufficient.

Refer to the Reliance Guideline – SAHPGL-BAU-01 for information on evaluation pathways.

3.9 SAHPRA’s Recognised Regulatory Authorities

Refer to the Reliance Guideline – SAHPGL-BAU-01 for information on the RRAs with which SAHPRA aligns
itself and collaborative procedures.
The collaborative procedure must be clearly stated in the cover letter (Module 1.0.1) of the Application,
e.g., Generic – Zazibona or NCE – M4ALL.

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3.10 Expedited review process

Refer to the latest version of HPA03-2022/23 Priority Review Requests Communication.

In addition to the provisions given in the relevant Priority Review Requests Communication, a clear
indication of priority review request approval must be clearly stated in the cover letter (Module 1.0.1) of
the application.

3.11 Medicines for Use in a Public Health Emergency (PHE)

Refer to the latest version of the guideline, SAHPGL-PEM-01, 'Availability of Medicines for Use in a PHE'.

3.12 Fees

The fees payable are published in the Government Gazette and are also available on the SAHPRA website.
Refer to SAHPGL-FIN-01 SAHPRA Payment Guideline for the details of the payment of fees to SAHPRA.

Note
The only valid payment evidence to be included in M1.2.2.1 should be proof of payment from the
applicant’s bank. The Proof of Payment must consist of the Sales Order reference as generated on the
SAHPRA Engagement Portal.
On the notification of registration via email, the applicant must submit a closing sequence that includes
the final signed PI and PIL reflecting the approved proprietary name(s), registration number(s) and
registration date as stated in the email. Proof of submission of the closing sequence must be sent to
[email protected]. Proof of payment of the registration fee must be submitted via the
SAHPRA Engagement Portal. The new registration certificate(s) will be issued via the SAHPRA Engagement
Portal once the compliant proof of payment has been received.

Note that the PI and PIL submitted in the closing sequence must be the approved version with only the
changes specified in the paragraph above.
For veterinary medicines, on notification of registration, the registration fee proof of payment, from the
applicant’s bank, and the final, signed PI and PIL (reflecting the approved proprietary name(s), registration
number(s) and registration/version date) should be submitted to SAHPRA in one email via the relevant
mailbox: [email protected].

3.13 Same or separate applications

For the purposes of registration, the following products will be regarded as either being the same product
or separate product applications.

Application

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TYPE OF Same Separate

APPLICATIONS
3.13.1 Each individual dosage form of a particular medicine X

3.13.2 Variations of the active pharmaceutical ingredient (API) of a product X

3.13.3 Tablets/Capsules/Suppositories/Lozenges
a) Different pack-sizes of the same strength and formulation. X
b) Different strengths and formulations. X
c) Uncoated and coated tablets of the same strength and formulation. X

3.13.4 Syrups/Liquids/Solutions (excluding parenterals)/Creams/Ointments

a) Different container sizes of the same strength and formulation. X

b) The same container size of different strengths and formulations. X

Application
TYPE OF
APPLICATIONS Same Separate

3.13.5 Ampoules and Vials and Large Volume Parenterals

a) Ampoules or single-dose vials containing identical solutions of the same X
strength but of different volumes (i.e., resulting in different total
doses). containing solutions of different strengths.
b) Ampoules X
c) Ampoules and single-dose vials containing, e.g., dry powder, crystals of X
different masses.
d) Ampoules and single-dose vials containing the same respective masses X
of e.g., dry powder, crystals.
e) Ampoules, single-dose vials, as well as pre-filled disposable syringes X
and cartridges containing identical solutions of the same strength and
same volume of liquid.
f) Dental cartridges containing different volumes of fluids of the same X
strength (provided the dose remains constant).
g) Ampoules containing “water for injection”, but of different volumes. X
h) Special ampoules of dry powder and “water for injections” contained X
in the same unit but intended for mixing at the time of injection if
water for injections is fully described in dossier.

i) Ampoules containing identical solutions of different volumes are used X

only as diluents in the reconstitution of a preparation for parenteral
use. use.

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j) Multidose vials containing different volumes of the same strength X

and formulation with the same dosage schedule.
k) Multidose vials and a single-dose ampoule or vial of the same X
formulation if the single-dose ampoule or vial corresponds to the dose
indicated for the multidose vial.
l) Multidose vials containing dry powder of different mass of the s a m e X
formulation, and the same concentration when reconstituted.
m) An ampoule of diluent packed together with any preparation, including X
biological medicines, if the diluent is fully described in the dossier.
n) Infusion solutions of different volumes and of the same formulation, X
which are packed in containers of exactly the same type of material,
depending on the relevant information submitted.
o) Infusion solutions of the same formulation and of the same or different X
volumes, which are packed in containers made of different types of
materials.
p) A preparation, packed in plastic containers, intended to be marketed in X
glass containers containing the same volume and the same
formulation.
q) Products with the same strength and formulation but with different X
colours and/or flavours.

Application
TYPE OF
APPLICATIONS Same Separate

r) Applications containing the same API(s) applying for additional X

indications which render the product in a different scheduling status,
or different pharmacological classification, or have any other
restrictions imposed other than the original application.

s) Removal of antimicrobial preservative from single-dose presentation of X

registered vaccine that included a preservative in the original
approved formulation.

3.13.6 Same formulation with different proprietary names, whether of the same X
or different applicants

3.13.7 Clone or Replica applications X

3.14 Unregistered old medicines

Unregistered medicines that were on the South African market before registration became mandatory
with the promulgation of the Medicines and Related Substances Control Act, 1965 (Act 101 of 1965). These
medicines were never formally evaluated by the SAHPRA or former MCC for safety, efficacy and quality.

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The unregistered old medicines cannot be considered innovator products. The application must be
accompanied by documentary evidence (at least) of safety and efficacy to evaluate and determine whether
the product is safe and effective for the proposed dosage in the proposed population. This evidence must
also support the therapeutic indication(s) for which the applicant intends to market the product.

3.15 Clones and Replicas

The following requirements at the time of submission apply for the processing of clone and replica
applications:

a) Clones & Replicas submitted by the same applicant (replica-same)

i) The original application upon which the clone or replica is based, as sequence 0000 (if
not already submitted in eCTD to SAHPRA in eCTD format), and the clone or replica
application as sequence 0001.

ii) Declaration of Sameness for a clone or replica, signed by the applicant and endorsed by
a commissioner of oaths in M1.10 (amended template herewith included).

iii) Registration certificate for the registered product in M1.10

iv) List of proposed proprietary names or any prior approvals for Naming & Scheduling
received from the Authority in M1.0.

v) PI/PIL with new proprietary name(s) and application number(s).

vi) QIS/QOS document.

b) Replica products submitted by a different applicant (the HCR is different from the applicant)

i) A complete application as sequence 0000.

ii) Declaration of Sameness for a clone or replica, signed by the applicant and endorsed by
a commissioner of oaths in M1.10 (amended template herewith included).

iii) Letter of Permission from the applicant with the registered product allowing the second
applicant to use their data (template herewith included).

iv) Registration certificate for the registered product in M1.10.

v) List of proposed proprietary names with proof of any prior approvals for Naming &
Scheduling from the Authority.

vi) PI/PIL with new proprietary name(s) and application number(s) (for verification).
vii) QIS/QOS document.

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NOTES

1) Clone and replica applications may not be submitted with new variation or line extension
application(s) to the registered product(s) and/or when there is/are variation or line extension
application(s) to the registered product(s) in progress.

2) A clone/replica application must be identical to the registered product in every respect except the
proprietary name. Any other difference (other than the proprietary name) disqualifies the application
or product from being a clone or replica.

3.16 Variations Permitted during the Registration Process

All applications for registration in terms of Section 15 of the Act 101 are required to be complete in terms
of the eCTD and data requirements and no variations during the registration process are permissible except
for the following:
3.16.1 Transfer of Applicancy with motivation in exceptional circumstances sent to the
Inspectorate.
3.16.2 Urgent safety restriction updates as requested by or as deemed necessary by SAHPRA
or the applicant following consultation with SAHPRA.
3.16.3 Updated reliance documentation, e.g., where an RRA approval is obtained for the
product after the application was submitted to SAHPRA.

3.17 Permissible review response rounds and period for response submissions

3.17.1 Technical Screening

3.17.1.1 SAHPRA’s review process for screening will permit a maximum of one response round. If the
applicant fails to address the queries adequately, the application will be tabled for rejection.
3.17.1.2 Each response timeframe should be no longer than 30 working days from the date sent to the
applicant.
3.17.1.3 Extension of timelines for a response is not permitted.

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3.17.2 Evaluation Phase

3.17.2.1 The review process for new medicines will permit for all units a maximum number of two
response rounds. If the applicant fails to address the queries adequately by the second query
round, the application will be tabled for rejection from the respective unit.

3.17.2.2 First Query Round: each response timeframe should be no longer than 30 working days from
the date sent to the applicant.

Second Query Round: each response timeframe should be no longer than 30 working days
from the date sent to the applicant.

3.17.2.3 A letter of query should be responded to within 30 working days. Applicants may request an
additional period of up to 30 working days per response round. This request will only be
considered by the Authority if the applicant provides appropriate scientific justification. The
Authority will review the justification for the additional period. It will grant such a request in
writing to the Applicant, only if it is considered that this extension will enable the Applicant to
respond fully to the queries raised.

3.17.2.4 Note: If an applicant does not respond to the query referenced in 3.17.2.2 and does not
communicate any request for extension, this application will be tabled for rejection.

3.17.2.5 Applicants are encouraged to respond sooner than the expected response timeline.

3.18 Classification of Queries

The classification of queries is determined by the technical units and are defined as follows:

Minor queries

These relate to specific details or requests for clarification that do not significantly impact on the product’s
safety, quality, or efficacy. Typically, they involve editorial adjustments or minor administrative corrections
with negligible influence on the integrity of product data.

Moderate queries

These have the potential to impact quality and safety. If left unresolved or inadequately addressed, they
may compromise product standards. Reponses generally require supporting documentation or
clarification of less critical issues.

Major Queries

These directly affect the quality, safety, and efficacy of the product. They may result in delays with the
product approval and often necessitate substantial revisions to product information. Responses usually
involve comprehensive data analysis, re-evaluation, or submission of additional data.

Each subsequent round of queries issued by the relevant technical unit will explicitly categorise the
queries according to the severity and extent of unresolved concerns.

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3.19 Renewals

Refer to the latest version of the following documents:

• SAHPGL-HPA-04 Renewal of Human and Veterinary Medicines Requirements and Process
• Communication on Medicines Registration Renewals Implementation Framework
• Renewals Frequently Asked Questions (FAQs)

3.20 Cancellation or Withdrawal of Applications

HCRs of medicines and applicants should, before applying to the Authority, carefully consider any
decision to cancel or withdraw a registration or application for registration, as the Authority, after
consideration of all issues involved, has resolved the following with immediate effect.
Any medicine:
• of which the registration has been cancelled, or any “old medicine” of which the application for
registration has been withdrawn by notice in the Government Gazette, and
• for which a written application or request has been submitted by the holder of a certificate of
registration or by the applicant, to the CEO, will under no circumstances be reinstated.

The following relevant supporting documentation should be submitted:

• The letter that includes the motivation for the deregistration of the registered medicine or substance,
signed by the RP.
• Copy of the medicine registration certificate/affidavit.

When submitting a withdrawal during the evaluation process, the following information should be
attached:
• The applicant letter to request a withdrawal.
• Copies of the unit approval /recommendations for registration

Requests to cancel registrations or withdraw registration applications should be sent in a follow-up

sequence via the SAHPRA Engagement Portal. Refer to guideline 2.21 ZA-SAHPRA-eCTD-Specifications-
v3.1.
For the re-registration of the cancelled medicine, a new application for registration of a medicine must be
submitted in accordance with the requirements of the Act and the relevant Regulations.
An application for registration of a medicine may, at whatever stage of processing, be withdrawn by
written application to the CEO. The withdrawal shall under no circumstances be reversed once such an
application is approved and the approval confirmed in writing. A new application for registration must
be submitted should the applicant wish to proceed with registration thereafter.

4. REQUIREMENTS OF AN APPLICATION
Submission of new applications in eCTD (electronic Common Technical Document) format is mandatory
(excluding complementary and veterinary medicines).

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Specific guidelines also apply to the requirements for an application for complementary medicines.

5. PROPRIETARY NAME AND SCHEDULING OF SUBSTANCE AND MEDICINE

Refer to the current version of the Guideline for Proprietary Names for Medicines (SAHPGL-CEM-NS-03) and
Guideline to the Scheduling of Substance and Medicine (SAHPGL-CEM-NS-02).

6. MANUFACTURING REQUIREMENTS
Only medicines manufactured, packed and quality controlled at sites compliant with the current principles
of Good Manufacturing Practice (GMP) as prescribed by SAHPRA will be considered for registration.

SAHPRA's general policy is that the standard to be used to assess compliance with current Good
Manufacturing Practice (cGMP), is the South African Guide to Good Manufacturing Practice (SA guide to
GMP) (latest edition) (SAHPGL-INSP-02).

Under Section 22C of the Act, all South African manufacturers should be licensed (effective 2 May 2004).

isThese licensing requirements and standards aim to protect public health by ensuring that medicines meet
defined standards of quality and are manufactured in conditions that are clean and contaminant-free
conditions.

The Act requires that overseas manufacturers of medicine supplied to South Africa should comply with the
same or equivalent manufacturing standards as expected of South African manufacturers.

Evidence of compliance with Good Manufacturing Practices by the overseas manufacturer is required for
applications for the registration of imported medicines. When acceptable evidence of GMP compliance is
not available, overseas manufacturers are inspected by the GMP Inspectorate before registration of the
medicine is approved. SAHPRA reserves the right to request additional documentation, schedule an
inspection or reject any sites.

7. SAMPLES
All medicine applications for registration must include a sample of a unit pack, Section 15(1) of the Act.
Photographs of all dimensions of the sample in the final primary packaging and of the sample itself should
be included in the application on submission. SAHPRA may request a sample for testing and/or viewing
purposes.

8. STANDARDISED PROFESSIONAL INFORMATION WARNINGS AND

INFORMATION
Refer to the current version of Professional Information for Human Medicines: Standardised Texts Guideline
SAHPGL-CEM-04. This guideline should be read in conjunction with current pharmacovigilance
recommendations for the medicine.

9. RESPONSIBILITIES OF EACH UNIT

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9.1 Pharmaceutical Evaluations Management (PEM) Sub Programme 4 consists of the following
sub-units.
9.1.1 The PEM Pre-Registration Sub-Unit (also referenced as the Quality Unit PEM) is responsible for
the evaluation of all new registrations (small molecules) in terms of:
a) Quality of the drug substance (API) and drug product (finished pharmaceutical product).

9.1.2 The PEM Post Registration Sub-Unit (also referenced as the Quality & Bioequivalence (Q & BE)
Variations Unit) is responsible for the evaluations of variations to registered products (small
molecules) in terms of:

a) Quality of the drug substance (API) and drug product (finished pharmaceutical product).
b) Bioequivalence of generic medicines to their innovator counterparts.

9.1.3 The Complementary Medicines Sub-Unit is responsible for:

a) Evaluation and review of applications for the registration of Complementary Medicines.
b) Receiving and collating initial and subsequent responses.
c) Evaluation and review of applications for the amendment of the register for
Complementary Medicines
d) Issue licenses for the manufacture, imports, exports, wholesale and distribution of
Complementary Medicines.

9.1.4 The Biologicals Sub-Unit is responsible for:

a) Biological new registration applications and responses to resolutions, and matters about
biological medicines during review for registration.
b) Evaluation of technical changes to registered biological medicines and “old” biological
medicines.
c) Evaluation of clinical aspects of the Professional Information and relevant changes to
Professional Information for biological medicines.
d) Technical support to other units with respect to biological matters.

Note: For Biologicals:

• For any activities not described above, the applications and/or queries should be directed to (and
properly coded for) the relevant Units.
• Relevant supportive documentation should be attached as per the Modules/Sections described
in the relevant CTD format.

9.1.5 Veterinary medicines Sub-Unit

Refer to SAHPGL-PEM-VET-04 Guideline for Registration of Veterinary Medicines for information on

Veterinary product applications.

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9.2 Programme 3 - Inspectorate and Regulatory Compliance (IRC)

The Inspectorate and Regulatory Compliance is responsible for:
a) Inspection and evaluation of sites for the manufacturing, packing, and testing of
medicines nationally and internationally, as well as inspection and evaluation of all
storage and distribution sites for medicines.
b) Investigation of complaints regarding registered and unregistered medicines.
c) Monitoring compliance with the Act and prosecution in case of non-compliance.
d) Monitoring the importation and exportation of medicines in consultation with customs
authorities.
e) Licensing of manufacturers, importers and exporters of orthodox medicines.

9.3 Sub-Programme 4 - Clinical Evaluations and Management (CEM)

9.3.1 The Clinical Evaluation Unit is responsible for:
a) Evaluation of clinical and pre-clinical data.
b) Evaluation of clinical aspects of the Professional Information and relevant changes to
Professional Information.

c) Evaluation of proprietary names and schedules.

d) Evaluation of prescribing rights by authorised prescribers and changes thereto.
e) Evaluation of bioequivalence of Generic medicines to the innovator counterparts.

9.3.2 The Clinical Trials Unit is responsible for the evaluation of:
a) Clinical trial applications and clinical trial amendments.
b) Reports of adverse events arising from a clinical trial.

9.4 Programme 2 - Health Products Authorisation (HPA)

Health Products Authorisation is responsible for the following:
a) Receiving applications for registration of medicines and variations.
b) Screening of new human medicine applications.
c) Certification of new registrations, applicant transfers and proprietary name changes.
d) Cancellations of registered medicines and withdrawal of applications for the registration of
medicines.

e) Communication of queries to applicants.

10 REFERENCES
The following related documents are referenced:

10.1 SAHPGL-CEM-01 Clinical Guideline

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10.2 SAHPGL-CEM-02 Guideline for Professional Information for Human Medicines

10.3 SAHPGL-CEM-03 Guideline for Patient Information Leaflet for Human Medicines

10.4 SAHPGL-CEM-04 Standardised Texts Guideline

10.5 SAHPGL-HPA-04 Renewal of Human and Veterinary Medicines Requirements and processes

10.6 SAHPGL-PEM-01 Availability of medicines in a Public Health Emergency (PHE)

10.7 SAHPGL-BAU-01 Reliance Guideline

10.8 2.21 SAHPRA eCTD Specification 3.1

10.9 SAHPGL-HPA-03 eCTD Validation Criteria

10.10 SAHPGL-PEM-02 Quality and Bioequivalence Guideline

10.11 SAHPGL-INSP-02 Guideline for Good Manufacturing Practice

10.12 17.05 Payment Guideline

11 VALIDITY
This guideline is valid for a period of five (5) years from the effective date of revision and replaces the General
Information Guideline, 2.01. It will be reviewed on this timeframe or as and when required.

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