TASK 2 Due Diligence

Module: 1.
0 Due diligence Report
For all the questions you answered NO, list the question number and a statement indicating the
information that is required
No. Deficiency Statement Accountability Priority
SAHPRA’s RECOGNISED REGULATORY AUTHORITIES
33 European Medicines Agency Centralised Procedure (EMA SOUTH AFRICA B

CP)
34 European Medicines Agency Decentralised Procedure (EMA SOUTH AFRICA B

DCP)
35 Health Canada SOUTH AFRICA B
36 Medicines and Health Products Regulatory Agency (MHRA), SOUTH AFRICA B

UK
37 Ministry of Health, Labour and Welfare (MHLW), Japan SOUTH AFRICA B
38 Swiss Agency for Therapeutic Products (Swissmedic) SOUTH AFRICA B
39 Therapeutic Goods Administration (TGA), Australia SOUTH AFRICA B
40 US Food and Drug Administration (US FDA) SOUTH AFRICA B
1.0 LETTER OF APPLICATION
136 The letter should include Registration number or Application SOUTH AFRICA B
number
137 The letter should include Sequence number SOUTH AFRICA B
MANUFACTURING, PACKAGING AND TEST SITES
188 The license number should be provided INDIA B
189 The date of issue of the license should be provided INDIA B
190 If a license number is not available for a foreign site, the INDIA B
details of the GMP certificate issued in terms of WHO
certification scheme should be provided.
199 It should be confirmed that copies of the latest GMP SOUTH AFRICA B
certificate for manufacturer/s and packer/s or a copy of the
appropriate manufacturing licence/s I include in in section
1.7.3
DECLARATION AND SIGNATURE
215 The application should be dated SOUTH AFRICA B

Module: 1.3.1.1 Due diligence Report
1.3.1.1 PI (PROFESSIONAL INFORMATION)
Confirmation should be included to confirm that the printed PI

4 SOUTH AFRICA B
will comply with regulation 11 in terms of legibility.
5 It should be confirmed that the language, spelling and SOUTH AFRICA B

grammar, punctuation and editorial correctness in the PI text
have been checked thoroughly before submission of the
application.
The date of submission should be included on each page.
6 SOUTH AFRICA B
7 Each page of the PI should be initialled by the pharmacist SOUTH AFRICA B

authorised to communicate with the authority on behalf of the
company (electronic initials are allowed).
The word “medicine” should be used for the product and not
9 SOUTH AFRICA B
the word “drug” or “medicinal product” or “agent”.
The PI should be provided to the Authority electronically in
11 SOUTH AFRICA B
both MS Word and PDF format.
Every statement or if applicable paragraph should be verified
20 SOUTH AFRICA B
by a reference.
24 An electronic copy (Word document) on diskette or CD of the SOUTH AFRICA B
PI should be included if the submission is in paper.
HEADING TO BE USED ACCORDING TO GUIDELINE 2.6

4.4 Special warnings and precautions for use
39 SOUTH AFRICA B
Paediatric population
4.5 Interaction with other medicines and other forms of
40 SOUTH AFRICA B
interaction
Additional information on special populations
4.8 Undesirable effects
43 SOUTH AFRICA B
Summary of the safety profile
Tabulated list of adverse reactions
Description of selected adverse reactions
Other special populations
5.2 Pharmacodynamic properties
47 SOUTH AFRICA B
a) General introduction
b) General characteristic
 Absorption
 Distribution
 Biotransformation
 Elimination
 Linearity/non-linearity
c) Characteristics in specific Groups
d) Pharmacokinetic/pharmacodynamic
relationship(s)
SPECIFIC REQUIREMENTS FOR DIFFERENT DOSAGE FORMS
94 In the case of a medicine for oral administration which SOUTH AFRICA B

contains or does not contain sugar, the warning: “contains
sugar” or “sugar free”, whichever is applicable, should be
included.
106 A visual description of appearance of the product (colour, SOUTH AFRICA B

markings, etc.) should be given, in a separate paragraph to
the standard term, including information on the actual size of
a solid oral formulation, e.g. ‘Tablets, white, circular, flat,
bevelled-edge tablets of 5 mm marked ‘100’ on one side’
4 CLINICAL PARTICULARS
4.1 THERAPEAUTIC INDICATIONS
122 Advice on action to be taken if one or missed dose(s) is (are) SOUTH AFRICA B
missed, or e.g. in case of vomiting. (the advice should be as
specific as possible, taking into consideration the
recommended frequency of dosing and relevant
pharmacokinetic data)
123 Advice of preventative measures to avoid certain adverse SOUTH AFRICA B

reactions should be provided. (e.g. administration of
antiemetics) with cross-reference to section 4.4,
124 The intake of the product in relation to fluid and food intake, SOUTH AFRICA B
together with a cross-reference to section 4.5 in case of
specific interaction e.g. with alcohol, grapefruit or milk should
be stated.
125 Advice regarding repeat use, with any information on intervals SOUTH AFRICA A
to be observed between courses of treatment, as appropriate,
should be stated.
PAEDIATRIC POPULATION
143 The statement <Currently available data are described in SOUTH AFRICA B
section <4.8><5.1><5.2> but no recommendation on a
posology can be made > should be included or
144 The statement X should not be used in children aged x to y SOUTH AFRICA B
<years, months><or any other relevant subsets e.g. weight,
pubertal age, gender >because of <safety><efficacy>
concern(s) to be stated with cross-reference to sections
detailing data (e.g. 4.8 to 5.1) > should be included or
145 The statement there is no relevant use of X in <the paediatric SOUTH AFRICA B
population><in children aged x to y><years, months>><or any
other relevant subsets e.g. weight, pubertal age, gender> in
the indication(s) <specify indication(s). should be included or
146 The statement X is contraindicated in children aged x to SOUTH AFRICA B

y><years, months> <or any other relevant subsets e.g.

weight, pubertal age, gender> < in the indication …>
4.3 CONTRAINDICATIONS
155 The patient populations/special populations not studied in SOUTH AFRICA B

clinical trials must be contraindicated
156 Patients populations/special populations excluded from SOUTH AFRICA B

clinical trials for safety and/or other reasons must be
contraindicated
159 Where for safety reasons, the product should be SOUTH AFRICA B
contraindicated in a specific population it should appear in the
section with a cross-reference to the section giving detailed
information on the safety issue.
160 A contraindication in the paediatric population should be listed SOUTH AFRICA B

without a subheading.
161 Porphyria, if absolutely contraindicated should be listed. SOUTH AFRICA B

(Cross-reference to section 4.4)
4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE
167 Serious adverse reaction to which healthcare professionals SOUTH AFRICA B

need to be alerted
168 Any measures which can be taken to identify patients at risk SOUTH AFRICA A
and prevent the occurrence or detect early the onset or
worsening of noxious conditions
174 Any particular risk associated in incorrect route of SOUTH AFRICA B

administration
4.5 INTERACTION WITH OTHER MEDICINES AND OTHER FORMS OF INTERACTION
187 Interactions referred to in other sections of the PI should be SOUTH AFRICA B

described and cross-referenced from the other sections
188 Additional information on special populations should be SOUTH AFRICA B

included if the impact is more severe
189 Information specific to paediatric population SOUTH AFRICA B
4.6 FERTILITY
193 Pregnancy non-clinical data SOUTH AFRICA B

Comprehensive information on relevant adverse events
reported in the embryo, the foetus, neonates, delivery/birth
process and pregnant women, when appropriate
196 Cross references should be included in the section 4.3 SOUTH AFRICA B
contraindications
4.7 EFFECTS ON ABILITY TO DRIVE AND USE MACHINES SPECIFIY WHETHER THE
MEDICINES HAS
202 Duration of the impairing effect and development of tolerance SOUTH AFRICA B
or adverse reactions with continued use must be should be
included
4.8 UNDERSIABALE EFFECTS
206 Are ADR’s from clinical trials, post authorisation safety studies SOUTH AFRICA B
and spontaneous reporting for which after a thorough
assessment, a causal relationship between the medicine and
the adverse event is at least a reasonable possibility should
be included
a) DESCRIPTION OF SELECTED ADVERSE REACTIONS
211 Information on a specific ADR which may be useful to SOUTH AFRICA B

prevent, assess or manage the occurrence of an adverse
reaction in clinical practice
212 A paediatric sub section should always be included (unless SOUTH AFRICA B
irrelevant)
213 Special populations should be included SOUTH AFRICA B
214 For data from sources other than clinical trials/studies data: SOUTH AFRICA B
the term “frequent” or “less frequent” should be use
215 For a MSM professional information without its own clinical SOUTH AFRICA B
trial, ADRS should be categorised according to the frequency
classification “Frequent” and “Less frequent”
220 Information specifically observed in special populations such SOUTH AFRICA B

as elderly, patients with renal impairment, patients with
hepatic impairment, other concomitant diseases should be
included.
221 If there are any specific paediatric considerations, there SOUTH AFRICA B
should be a subsection entitled ‘paediatric population’
222 Special mention should be made of those medicine/strength SOUTH AFRICA B

of a formula for which ingestion of only one dose unit by
children can cause fatal poisoning
5.2 PHARMACOKINETIC PROPERTIES
238 Biotransformation: degree of metabolism; which metabolite; INDIA A

activity off metabolites and contribution to affect and toxicity;
enzyme involved in metabolism; site of metabolism; results
from in vitro introduction studies that indicate whether the new
compound can induce/inhibit metabolic enzymes
239 Elimination: elimination half-lives, total clearance; enter and/or INDIA A

intra-subject variability in total clearance; excretion routes of
the unchanged substance and metabolites including the
relative portion of the hepatic and renal elimination fraction,

involvement of transport proteins
240 Linearity/nonlinearity: linearity/non-linearity of INDIA A

pharmacokinetics of the active substance which respect to
dose and/or time; if the pharmacokinetics are non-linear with
respect to dose and/or time, the underlying reasons for the
non-linearities should be presented
241 Relationship between dose/concentration/pharmacokinetic INDIA A

parameter and effect (either true endpoint, validated surrogate
endpoint or side-effect) should be provided
5.3 PRE-CLINICAL SAFETY DATA
245 Environmental risk assessment (ERA) to be included only SOUTH AFRICA B

when indicated by SAHPRA and reference to 6.6
6 PHARMACEUTICAL PARTICULARS
6.3 SHELF LIFE
260 The storage instructions should indicate storage SOUTH AFRICA B

temperatures, humidity and exposure to light.
265 Recommended temperature range and maximum duration of SOUTH AFRICA B

temporary storage should be specified
266 Action to be taken after the product has been stored under the SOUTH AFRICA B
temporary storage condition (e.g. discard immediately) should
be included
270 If the product is presented in a blister pack, and the SOUTH AFRICA B
recommendation states to protect from light, the instruction
not to remove the blister pack from the carton tell required for
use, should be included
6.6 SPECIAL PRECAUTIONS FOR DISPOSAL OF THE USED MEDICINE OR WASTE

MATERIALS DERIVED FROM SUCH MEDICINE <AND OTHER HANDLING> OF THE
PRODUCT
288 A cross-reference in section 4.2 to the relevant information in SOUTH AFRICA B

section 6.6 could be included e.g. ‘For instructions on dilution
of the product before administration, see section 6.6’
291 Information on risks due to occupational exposure should be SOUTH AFRICA B

included in this section, with reference to section 4.4 or 4.8
Module:1.3.1.2 Due diligence Report
1.3.1.2 STANDARD REFERENCE MULTISOURCE MEDICINES
306 Information obtained from other RRAs, e.g. Rapporteur’s SOUTH AFRICA B
reports
307 SAHPRA monograph for “old medicines” SOUTH AFRICA B
308 Other references or information from peer-review journals SOUTH AFRICA B
309 Martindale: The Complete Drug Reference (For safety SOUTH AFRICA B
information only, not for efficacy)
Module:1.3.2 Due diligence Report
1.3.2 PATIENT INFORMATION LEAFLET
1 Confirmation that the printed PIL will comply with the legibility SOUTH AFRICA B
requirements of Regulation 12 of Act 101 and the PIL
Guideline should be included
2 Should be confirmed that the PIL will be translated into one of SOUTH AFRICA B
the official language if not already translated
3 It should be concerned that the PIL translation will be SOUTH AFRICA B

validated, prior to being made available to consumers
4 The declaration should confirm that the PIL has been checked SOUTH AFRICA B
for spelling and grammatical correctness
8 PIL should be reference to the PI for each statement in the SOUTH AFRICA B
PIL
10 Reference to the exact page/s in the Professional information SOUTH AFRICA B

should be included
Module:1.3.3 Due diligence Report
1.3.3 LABEL
27 A declaration that the printed label will comply with SOUTH AFRICA B
regulations 10 in terms of legibility should be included
34 All medicines, the ATC17 classification of medicine should be SOUTH AFRICA B

in
48 The outer label should include a barcode suitable for the SOUTH AFRICA B
identification and the tracking of the medication
Module:1.4 – 1.13 Due diligence Report
1.7.7 SAPC REGISTRATION
73 Is there are primary and secondary Packers this should be SOUTH AFRICA B
clearly indicated on the flow diagram
1.10 FOREIGN REGISTRATION
92 1.10.3 A copy of the foreign professional and patient INDIA B

information should be furnished for at least the country of
origin and doors recognised authorities, if registered in any of
the of these countries
94 1.10.4 A summary of the similarities/differences in the data SOUTH AFRICA B

packages submitted in other countries should be included
Module:2 Due diligence Report

2.3 QUALITY OVERALL SUMMARY
17 The Quality Overall Summary – introduction should be SOUTH AFRICA B

provided
18 The introduction should include the proprietary name, non- SOUTH AFRICA B
proprietary name or common name of the drug substance,
company name, dosage form(s), strength(s), route of
administration and proposed indication(s)
Module:3.2.S Due diligence Report
3.2.S CEP OR CPQ
7 3.2.S.5 Reference standards or materials of the FPP INDIA B

manufacturer and complete section 3.2.S.5
8 3.2.S.6 Container closure system except where CEP SOUTH AFRICA B

specifies it and the applicant uses the same
11 3.2.S.1.3 General properties – API properties that are not INDIA B

controlled by the a API manufacturers specification
15 3.2.S.4.2/ 3.2.S.4.3 Analytical procedures and validation – for INDIA A

any methods used by the FPP manufacture in addition to
those in the API manufacturer’s specifications. Complete
section 3.2.S.4.2 and 3.2.S.4.3
17 3.2.S.5 Reference standards or materials of the FPP INDIA B

manufacturer and complete section 3.2.S.5
3.2.S.1.3 GENERAL PROPERTIES
33 The physical properties of the AP I should be provided INDIA B

(appearance, colour, physical state)
Solubilities over the physiological pH range (pH 1.2 to 6.8) in
36 INDIA A
mg/ml
41 If the API is hygroscopic, hygroscopicity should be discussed INDIA A
46 The melting point or range should be provided. INDIA A
47 Evidence of the occurrence of isomers (Chirality) should be INDIA A

addressed
If there are no isomers, this should be stated.
48 INDIA A
49 Evidence of the occurrence of polymorphs should be INDIA A

addressed.
50 If there are no polymorphs, this should be stated. INDIA B
3.2.S.2.6 MANUFACTURING PROCESS DEVELOPMENT

Information on the route of synthesis and purification of the
120 INDIA B
API should be provided.
State the solvents, used in the process, the step(s) at which
121 INDIA B
they are used, and the ICH class of the solvent.
State the reagent and or catalysts used in the manufacturing
122 INDIA B
process and the step(s) at which they are used.
The final steps of purification and / or crystallization, should
123 INDIA B
always specify the solvent used.
The scale of manufacture, the typical batch size, and the
124 INDIA B
maximum batch size (the range) for which the process is
described must be provided.
Alternate processes (if any) should be described with the
125 INDIA B
same level of details as the main process.
The impurity profile obtained from any alternate process must
126 INDIA B
be described.
If any reprocessing and/or reworking steps are performed,
127 INDIA B
they must be clearly described and if they are justified
Information on the fate and purging of all potential impurities,
128 INDIA B
including regioisomeric28 and stereoisomeric impurities, toxic
(including genotoxic) impurities.
Information on the fate and purging of residual solvents and
129 INDIA B
residues of catalysts in the starting material.
Discussion of manufacturing process development to support
130 INDIA B
a design space and/or real time release (if proposed).
Describe process development studies that provided the
131 INDIA B
basis for the design space(s) or which are used to justify
specifications, manufacturing parameters, etc.
Where PARs29 or a design space have been claimed in S.2.2,
132 INDIA B
studies which support the proposed ranges should be
described in S.2.6.
Studies conducted to assess criticality of process parameters
133 INDIA B
or material attributes identified in S.2.3 and/or S.2.4 should
also be described in S.2.6.
A description of the significant changes made to the
134 INDIA B
manufacturing process of the drug substance used in
producing nonclinical, clinical, scale-up, pilot, and, if available,
production scale batches should be provided.
A discussion of the significant changes made to the
135 INDIA B
manufacturing process of the drug substance used in
production scale batches should be provided
A description and discussion of the significant changes made
136 INDIA B
to the manufacturing site of the drug substance used in
production scale batches should be provided.
3.2.S.4.1 CONTROL OF ACTIVE PHARMACEUTICAL INGREDIENT

The specification should be dated and signed by authorized
165 INDIA B
personnel (i.e., the person in charge of the Quality Control
department or designate). (Electronic signatures are also
considered acceptable)
The specification reference number, version, and date for
166 INDIA B
version control purposes should be included.
Specifications should cover all the relevant quality parameters
169 INDIA B
such as identity, organoleptic, physical, chemical and
stereochemical properties, potency and microbiological
quality. Organoleptic properties may include appearance,
colour and clarity of solution. Physical properties may include
crystalline/polymorphic form, particle size distribution, specific
optical rotation, solubility, melting point, molecular weight.
The specifications should include reference to analytical
171 INDIA B
methods.
The physical and chemical properties of the active raw
172 INDIA B
material should be included.
A specification for the API as tested for by the FPP
173 INDIA B
manufacturer should be provided.
If the specification from the FPP manufacturer refers to a
174 INDIA B
recognised pharmacopoeia, it should be stated that the latest
edition is inferred.
The specification from the FPP manufacturer should be dated
175 INDIA B
and signed by authorized personnel (i.e., the person in
charge of the Quality Control department or designate).
(Electronic signatures are also considered acceptable)
The specification from the FPP manufacturer should have a

176 INDIA B
reference number, version, and date for version control
purposes should be included
If the specification from the API and FPP manufacturers is the
178 INDIA B
same a statement confirming this should be made.
ACTIVE RAW MATERIAL ADDITIONAL SPECIFICATIONS
If the active raw material is isomeric, the isomer should be
179 INDIA B
specified.
If the active raw material is polymorphic, the polymorphic form
180 INDIA B
should be specified.
If the active raw material contains impurities, this should be
185 INDIA B
specified.
3.2.S.4.2 ANALYTICAL PROCEDURES
Detailed methods used for quality testing by the manufacturer
186 INDIA A
(identification, assay related substances, residual solvents)
should be included or reference to the pharmacopoeial
monograph of a recognised pharmacopoeia should be made.
Detailed methods used for quality testing by the manufacturer
188 INDIA A
of the final product (identification, assay related substances,
residual solvents) should be included if different from that of
API manufacturer.
3.2.S.4.3 VALIDATION OF ANALYTICAL PROCEDURES
In-house methods require full validation.
190 INDIA A
Typical chromatograms from both the API manufacturer and
191 INDIA A
FPP manufacturer should be included.
If the method of assay is pharmacopoeial, system suitability
192 INDIA A
and linearity should be provided in place of full validation.
If an in-house method is used instead of the method of the
193 INDIA A
monograph, cross-validation data to demonstrate equivalence
of the methods should be submitted.34
If the method of the monograph is unsuitable to control
194 INDIA A
additional in-house impurities, an in-house method needs to
be developed and validated.
3.2.S.4.5 JUSTIFICATION OF SPECIFICATION
The API is pharmacopoeial is reference made to recognise
211 INDIA B
pharmacopoeia
The API is non-pharmacopoeia has full justification of the in-
212 INDIA B
house API stand it should be approved
A discussion should be provided on the inclusion or exclusion
213 INDIA A
of any tests, evolution of test, analytical procedures,
acceptance criteria, and any differences from compendial
standard should be discussed
3.2.S.5 REFRENCE STANDARDS OR MATERIALS
The batch number of the primary reference standard used
215 INDIA B
should be provided.
PHARMACOPOEIAL BASED ACTIVE INGREDIENTS
If a pharmacopoeial monograph is claimed for the API, it
216 INDIA B
should be confirmed that the pharmacopoeial reference
standard is used.
If a pharmacopoeial monograph is claimed and secondary
217 INDIA B
standards are used, it should be confirmed that the secondary
standard potency is established against the pharmacopoeial
primary standard.
If a pharmacopoeia monograph is cleaned and secondary
218 INDIA B
standards are used, it should be fully categorised to confirm
identity. (IR and UV spectra should be submitted for both the
primary and secondary reference standards run
concomitantly)
If a pharmacopoeial monograph is claimed and secondary
219 INDIA B
standards are used, a CoA should be provided
The batch number of the secondary (working) standard
220 INDIA B
should be provided.
3.2.S.7.3 STABILITY DATA
The results of stability studies performed on the API obtained
258 INDIA A
by the route of synthesis specified in 3.2.S.2.2 should be
included
WELL KNOWN CHEMICAL ENTITIES35
ACTIVE PHARMACEUTICAL INGREDIENTS DESCRIBED IN OFFICIAL PHARMACOPOEIA
INCLUDING A SPECIFICATION FOR DEGRADATION PRODUCTS AND WITHOUT STABILITY
DATA AND RETEST PERIOD: –
The suitability of the pharmacopoeial monograph should be
259 INDIA B
demonstrated for the particular name source. AND
The applicant specified in Section 1.7.4.1 that the API must
260 INDIA B
comply with the pharmacopoeia monograph immediately prior
to manufacture of the finished product. OR
A re-test period based on the results of long-term testing,
261 INDIA A
taking the results of testing under accelerated or, where
applicable, intermediate storage conditions, into consideration
should be proposed
WELL KNOWN CHEMICAL ENTITIES
FOR API MONOGRAPHS THAT DO NOT INCLUDE DEGRADATION PRODUCTS AND LIMITS 36
Stability data to support the specified retest period should be
263 INDIA A
included
The degradation pathways should be discussed.
264 INDIA A
WHEN DEGRADATION PATHWAYS ARE UNKOWN

The relevant data published in the literature to support the
265 INDIA A
proposed degradation pathways should be provided if
available
If no data on degradation pathways are available in the
266 INDIA A
scientific literature, including official pharmacopoeias, stress
testing should be performed.
Stress testing should be carried out on a single batch of the
267 INDIA A
API.
Stress testing should include the effects of temperatures in
268 INDIA A
(10C increments. (e.g., 50C, 60C, etc)) above that for
accelerated testing.
Stress testing should include the effect humidity (e.g., 75%
269 INDIA A
RH or greater)
Stress testing should include the effect of oxidation, on the
270 INDIA A
API
Stress testing should include the effect of photolysis, on the
271 INDIA A
API
Stress testing should evaluate photostability of the product
273 INDIA A
WHERE STABILITY DATA ARE REQUIRED AND PROVIDED37

STABILITY DATA RESULTS
The batch number should be stated.
274 INDIA B
The batch size should be stated.
275 INDIA B
The data should be generated from at least two pilot scale
276 INDIA A
batches.
The manufacturing site should be stated.
277 INDIA B
The container closure system should be stated.
278 INDIA B
The storage conditions should be stated.
279 INDIA B
The completed/proposed test intervals shown.
280 INDIA A
The stability data for the API stored in the proposed container
281 INDIA A
should include accelerated conditions.
The actual results of the studies should be presented.
282 INDIA B
Long-term results on at least two batches of the API stored
283 INDIA A
for a minimum period of six months at 25°2°C/605% RH
should be submitted, unless otherwise justified.38
Accelerated results derived from the well-known API material
284 INDIA A
stored for a minimum period of 3 months at 40°C2°C/75
5% RH should be submitted, unless otherwise justified.
BOTH WELL KNOWN AND NEW
Information on the analytical procedures used to generate the
302 INDIA A
stability data should be included.
A fully described stability-indicating assay used in the studies
303 INDIA A
and relative chromatograms should be included unless the
method for related substances is specific and quantitative
(HPLC).
A validation report should be included for the stability
304 INDIA A
indicating assay
Supporting chromatograms should be included in the
305 INDIA A
validation report.
A validation report should be included for the assay for
306 INDIA A
related substances if applicable.
RE-TEST BASED ON EXTRAPOLATED DATA
For API’s intended to be stored at room temperature, and
307 INDIA A
both long-term and accelerated data show little or no change
and little or no variability.
Extrapolation of the shelf life should be limited to up to twice
but no more than 12 months beyond the period covered by
long-term data.
For API’s intended to be stored at room temperature, and
308 INDIA A
long-term or accelerated data show change over time and/ or
variability.
Extrapolation of the shelf life should be limited to up to one
and a half times, but no more than 6 months beyond the
period covered by long-term data.
For API’s intended to be stored at room temperature with
309 INDIA A
data amenable to statistical analysis and supported by
statistical analysis and relevant supporting data,
Extrapolation of the shelf life should be limited to up to twice
but no more than 12 months beyond the period covered by
long-term data.
Module:3.2.P.1 Due diligence Report

3.2.P.1 DESCRIPTION AND COMPOSITION OF THE DRUG PRODUCT (NAME, DOSAGE

FORM)
26 If the moisture content or other characteristic of an API is INDIA B

relevant to the quantity of the IPIs used in the formulation, it
should be mentioned in a footnote.
27 If the quantity of an active ingredient is dependent on the

assay result, this should be explained in a footnote: “The
INDIA B
actual quantity of active will depend on the potency of the
active raw material: the excipients indicated by will be use to
adjust the bulk”
Module:3.2. P.2 Due diligence Report
3.2.P.2 PHARMECEUTICAL DEVELOPMENT

3.2.P.2.1 COMPONENTS OF THE FINISHED PHARMACEUTICAL PRODUCT
the following subsections should be included:
3 INDIA B
3.2.P.2.1 Components of the Pharmaceutical Product
3.2.P.2.1.1 Active Pharmaceutical Ingredient(s)
3.2.P.2.1.2 Excipients
3.2.P.2.2 Final pharmaceutical product
3.2.P.2.2.1 Formulation development
3.2.P.2.2.2 Overages
3.2.P.2.2.3 Physicochemical and biological properties
3.2.P.2.3 Manufacturing process development
3.2.P.2.4 Container closure system
3.2.P.2.5 Microbiological attributes
3.2.P.2.6 Compatibility
The report should contain a list of references.
6 INDIA B
3.2.P.2.2.1 FINAL PHARMACEUTICAL PRODUCT (NAME, DOSAGE FORM)

The tabulated comparison should include all excipients.
22 INDIA B
The tabulated comparison should include appearance.
23 INDIA B
The tabulated comparison should include physical
24 INDIA B
parameters.
The tabulated comparison should include impurity profile.
25 INDIA B
The report should include Pre-formulation testing
26 INDIA B
Module: 3.2.P.3 Due diligence Report
3.2.P.3.1 MANUFACTURER(S) (NAME, DOSAGE FORM)

The various stages of manufacturing and packaging at each
3 INDIA B
site should be clearly identified.
WHERE MORE THAN ONE PHARMACEUTICAL MANUFACTURING FACILITY/SITE IS
INVOLVED IN ANY OF THE MANUFACTURING OR PACKAGING PROCESS: –,
A declaration of similarity should be included in Module
6 SOUTH AFRICA B
1.5.2.3. .
If the methods are not the same, Module 3.2.P.2.3 should be
7 SOUTH AFRICA B
completed justifying the impact of the differences in process
3.2.P.3.2 BATCH FORMULA
13 The reference number and version number of the Master INDIA B

Document should be provided
3.2.P.3.3 DESCRIPTION OF MANUFACTURING PROCESS AND PROCESS CONTROLS
19 It should be checked that the narrative summary has been INDIA B

derived from the master manufacturing documents.
SPECIAL REQUIREMENTS
23 The flow diagram and narrative summary should indicate INDIA B

critical steps and points at which process controls,
intermediate tests or final product controls are conducted.
24 The Steps in the process should identify the appropriate INDIA B

process parameters, such as time, temperature, or pH
25 The process parameters should have associated numeric INDIA B

values presented as an expected range
26 Numeric ranges for critical steps should be justified in Section INDIA B

3.2.P.3.4.
The frequency with which the in-process check is done during
27 INDIA B
manufacture should be stated here or in 3.2.P.3.4.
All machine/equipment settings should be included (rotation
31 INDIA B
speeds, mixer speeds, oven settings, temperatures. autoclave
pressures etc.).
The duration of each treatment (e.g., mixing, milling, drying) in
32 INDIA B
each phase of the manufacturing process should be stated.
The time limit for completion of each phase of production
33 INDIA B
should be stated, as appropriate.
Yields (+Limits) should be provided at each stage of
37 INDIA B
manufacture and packing.
STERILE MANUFACTURING
The grades of clean areas should be indicated for
40 INDIA B
manufacture.
The grades of clean areas should be indicated for packaging.
41 SOUTH AFRICA B
3.2.P.3.5 PROCESS VALIDATION AND/OR EVALUATION

Critical equipment and process parameters should be
50 INDIA B
identified in the process validation report or protocol.
The holding time for the final product prior to packing should
56 INDIA B
be validated or included as part of the validation protocol.
Conditions during storage and/or shipping should be included
58 INDIA B
in the validation report or protocol.
CORRELATION WITH OTHER PARTS: 3.2.P.3
The critical controls given in 3.2.P.3.4 should reduce the risks
65 INDIA B
identified during formulation and process development in
3.2.P.2.3
Specifications and control methods should be listed in 3.2.P.4
66 INDIA B
for each raw material used in the manufacturing process.
Module: 3.2. P.4 Due diligence Report
3.2.P.4.1 SPECIFICATIONS
PHARMACOPOEIAL IPI’s
Recurrent pharmacopoeia requirements (BP, USP and Ph
5 INDIA B
Eur) are adhered to it is not necessary to list specifications.
Where it is indicated that the specifications does not
7 INDIA B
correspond to the latest edition of a recognise pharmacopoeia
but does appear in a previous edition, copies of the relevant
pharmacopoeial monograph submitted.
If the product is the subject of an individual Pharmacopoeial
7 INDIA B
monograph at least the final specified in the latest addition of
the pharmacopoeia should be met.

Specifications should be signed and dated regardless of
8 INDIA B
whether its pharmacopoeia or not.
The specifications should include reference to analytical
9 INDIA B
procedures and whether they are based on any known
monograph (i.e., pharmacopoeia reference or in-house
reference)
Is the product is the subject of an individual Pharmacopoeial
10 INDIA B
monograph and the requirements specified in the latest
edition of that pharmacopoeia have not been included,
departure from the monograph should be justified.
The analytical procedures should be signed, dated and
36 INDIA B
version controlled
3.2.P.5.3 VALIDATION OF ANALYTICAL PROCEDURES
SPECIAL REQUIREMENTS
If system suitability has been provided, the system suitability
56 INDIA A
data should address all aspects relevant to the method used
(for example tailing factor)
3.2.P.5.5 CHARACTERISATION OF IMPURITIES
The source and the quantity of the elemental impurities
69 INDIA B
introduce from each excipient should be listed
The total of each elemental impurities that are introduced
70 INDIA B
through all the excipients in the dosage form should be
provided
The total should be compared to the accepted limit per daily
71 INDIA B
dose
If the total elemental impurity level from all sources in the drug
72 INDIA B
product is expected to be consistently less than 30% of the
permitted daily exposure (PDE) then additional controls are
not required
3.2.P.6 REFERENCE STANDARDS OR MATERIALS

If a pharmacopoeial monograph is claimed the
7 INDIA B
pharmacopoeial reference standard should be used
If a pharmacopoeial monograph is claimed the
8 INDIA B
pharmacopoeial reference standard should be used
If a secondary standard/working standard is used, the
9 INDIA B
potency should be established against the
pharmacopoeial/primary standard
The origin and batch number of the working standard should
13 INDIA B
be included
3.2.P.7 CONTAINER CLOSURE SYSTEM

A full specification of the closure system (titles & limits) should
2 SOUTH AFRICA B
be given including the nature of the material, & dimensions
A description of the pack size should be provided including
8 SOUTH AFRICA B
number of units or volume, type of packaging material, colour
and nature and colour of closure
A description of each of the control procedures performed by
10 INDIA B
the manufacturer of the final product should be provided
GENERAL DETAILS REQUIRED FOR IMMEDIATE CONTAINERS
The capacity of each container should be specified.
19 SOUTH AFRICA B
CORRELATION WITH OTHER PARTS

The specified containers should correspond to those reflected
24 SOUTH AFRICA B
in the PI with regard to presentation sizes.
BLISTER PACKS/STRIP PACKS/POUCHES
The appearance of each blister component should be
84 SOUTH AFRICA B
specified (to include the surface (finish), absence of holes,
cracks, creases, scratches etc).
The grade of each component material should be specified
85 SOUTH AFRICA B
ALUMINUM FOIL
The porosity of Aluminium foil; should be specified
89 SOUTH AFRICA B
The grade of the plastic should be specified.
90 SOUTH AFRICA B
The shape and size of the bubble or the pocket in which the
93 SOUTH AFRICA B
dosage for is placed, should be specified
The moisture content of the coach of plastic film should be
94 SOUTH AFRICA B
specified.
The adhesion of the plastic/film laminate should be specified
95 SOUTH AFRICA B
The chemical nature of the heat seal coating which is in
98 SOUTH AFRICA B
contact with the dosage form should be specified
The heat seal bond strength, intactness of the blister or
100 SOUTH AFRICA B
integrity of the seal should be specified. 3.2.P.3 may be
referred to
DESICCANT
The inertness should be specified
142 SOUTH AFRICA B
It should be indicated how the desiccant is packed
143 SOUTH AFRICA B
The inertness of the packaging of the desiccant should be
144 SOUTH AFRICA B
specified
The presentation size should be specified. (e.g., mass of
145 SOUTH AFRICA B
sachet/capsule)
The efficiency of the desiccant should be specified.
146 SOUTH AFRICA B
WADDING
The type of wadding should be specified.
148 SOUTH AFRICA B
The inertness of the wadding should be specified.
149 SOUTH AFRICA B
The appearance of the wadding should be specified
150 SOUTH AFRICA B
The colour should be included in the description
151 SOUTH AFRICA B
If the wadding is coloured, the colourant should be specified.
152 SOUTH AFRICA B
If the wadding is coloured, the non-toxicity of the colourant
153 SOUTH AFRICA B
should be confirmed
If the wadding is bleached, the absence of the bleaching
154 SOUTH AFRICA B
agent should be specified.
The cleanliness of the wadding should be specified.
155 SOUTH AFRICA B
The microbiological purity of the wadding should be
156 SOUTH AFRICA B
confirmed.
3.2.P.8.1 STABILITY SUMMARY AND CONCLUSION

The table should indicate clearly the packaging material used
4 INDIA B
The table should indicate clearly the manufacturer of API.
5 INDIA B
The table should indicate clearly the API batch number used.
6 INDIA B
3.2.P.8.2 POST-APPROVAL STABILITY PROTOCOL AND STABILITY COMMITMENT

The post-approval stability commitment to ongoing monitoring
18 INDIA B
of batches should be signed and dated
A commitment to continue stability trials on the primary
19 INDIA B
batches up to the end of the proposed shelf life should be
provided if initial data are only are submitted (NCE 12 months
or MSM 9 months)
3.2.P.8.3 STABILITY DATA
Information on the analytical procedures used to generate the
21 INDIA B
data should be included
If the analytical procedures are located in 3.2.P.5.2., then they
22 INDIA B
may be referred to
Validation of the procedures should be included in 3.2.P.8 .3
23 INDIA B
all located in, 3.2.P.5.3 and referred to
The assay method must be shown to be stability indicating,
24 INDIA B
3.2.P.5.3 may be referred to
Information on characterisation of degradation impurities
25 INDIA B
should be included unless located in 3.2.P.5.5
BOTH NCE’s AND GENERICS
It should be confirmed that the primary stability data were
26 INDIA B
derived from the formulation being applied for 3.2.P.1
It should be confirmed that the primary stability data were
27 SOUTH AFRICA B
derived from product packaged in the proposed packaging
material included in 3.2.P.7.
It should be confirmed that each active raw material used in
28 INDIA B
the manufacture of the batches of the product controlled in
stability was manufactured by the manufacturer/s being
applied for in 3.2.S.
It should be confirmed that the analytical methods remained
29 INDIA B
the same during the stability trial
If a chromatographic system is employed to determine the
31 INDIA B
content of degradation products, it should be confirmed that
the system is capable of separating and detecting compounds
which are likely to be present as impurities or which may arise
via established degradation pathways.
PRODUCTS CONTAINING WELL-KNOWN CHEMICAL ENTITIES
NUMBER OF BATCHES/BATCH SIZES/CONDITIONS/PERIOD OF TESTING REQUIRED:
At least 3 months data on two batches of product stored at
40 INDIA A
accelerated/stress conditions (40ºC±2ºC / 75%RH±5%, or 15
ºC above the proposed long term storage temperature)
should be included at the time of submission.
If the product is a tablet or capsule one batch should be at
41 INDIA B
least pilot scale (1/10th of production size or at least 100000
units, whichever is the largest) the second may be smaller but
not laboratory scale)
PRESENTATION OF STABILITY DATA
It should be confirmed in each case whether the stated
53 INDIA B
conditions were controlled.
The source of the active raw materials used in each batch
60 INDIA B
reported on should be stated.
The pack-size and the container in which the dosage form
61 SOUTH AFRICA B
was packed should be stated.
The source and quantity of the elemental impurities
69 INDIA B
introduced from each excipient should be listed.
78 Product is sensitive to heat, the stability studies should be INDIA B
conducted at an alternative lower temperature condition
(designated long-term storage temperature)
85 If the product is a solid dosage form, stability data should be SOUTH AFRICA B
obtained from at least the smallest and largest of each
container-closure system proposed for marketing
TABLETS
120 The appearance should be described including colour, shape, SOUTH AFRICA B
odour
122 If the tablet is uncoated, hardness should be specified SOUTH AFRICA B
123 If the tablet is uncoated, friability should be specified SOUTH AFRICA B
Module: 3.2.R.1 Due diligence Report
3.2.R.1.4.1 DISSOLUTION STUDIES, DATA AND REPORTS

The product is a solid dosage form the dissolution profiles of
88 SOUTH AFRICA B
the test and reference production should be included
The application for a BCS biowaiver, comparative dissolution
91 SOUTH AFRICA B
between test and reference product should be provided.
DISSOLUTION REPORT FOR ALL DISSOLUTION STUDIES
The batch number, manufacturing/expiry date, packaging
96 SOUTH AFRICA B
should be provided for the test product.
The dissolution method should be described.
101 SOUTH AFRICA B
The dissolution method should be specified in-line filtration for
102 SOUTH AFRICA B
drawing the dissolution samples to ensure that the dissolution
of the sample is stopped immediately on withdrawal of the
sample unless filtration is demonstrated to be unnecessary.
There should be a discussion and conclusion.
110 SOUTH AFRICA B
The date of analyses should be included.
111 SOUTH AFRICA B
The date on which the report was written should be included.
112 SOUTH AFRICA B
There should be a GMP/GLP compliance, declaration by the
113 SOUTH AFRICA B
laboratory performing the analyses.
Reference should be provided regarding the availability of
114 SOUTH AFRICA B
validation records of test methods and procedures for and
records of the calibration of instruments and maintenance of
equipment.
REQUIREMENTS FOR A BCS BIOWAIVER
Data to demonstrate human absorption should be included.
118 SOUTH AFRICA B
The API in the test protest is identical to that of the reference
120 SOUTH AFRICA B
product.
If a BCS III by a waiver is applied for, the test and the
122 SOUTH AFRICA B
reference products contain qualitatively the same and
quantitatively very similar excipients.
A description of the function of the excipients should be
123 SOUTH AFRICA B
included.
A justification whether the amount of each excipient is within
124 SOUTH AFRICA B
the normal range should be provided.
Excipients that might affect bioavailability, e.g., Sorbitol,
125 SOUTH AFRICA B
mannitol, sodium lauryl or other surfactants should be
identified.
For excipients that might affect bioavailability their possible
127 SOUTH AFRICA B
impact on and susceptibility to interactions with API (e.g.,
complexation) should be addressed
For excipients that might affect bioavailability the possible
128 SOUTH AFRICA B
impact on API permeability should be addressed
For excipients that might affect bioavailability the possible
129 SOUTH AFRICA B
impact on interaction with membrane transport is should be
addressed
A motivation for the BCS biowaiver should be submitted.
130 SOUTH AFRICA B
The motivation should adjust the appropriateness of the
131 SOUTH AFRICA B
biowaiver that is i.e., confirmation with supporting references,
that no characteristic which requires in in vivo bioequivalence
study is applicable.
In addressing the appearance of the BCS biowaiver, the
132 SOUTH AFRICA B
benefit risk balance/ ratio, clinical indications, food affect and
any other relevant aspect should be included.
3.2.R.1 RESULTS
Dissolution should be performed in three dissolution media
137 INDIA A
i.e., pH 1,2; 4,5 and 6,8
Dissolution should be greater that 85% in 390 minutes or less
138 INDIA A
in each of the following three media: pH 1.2 HCl, pH 4.5
buffer, pH 6.8 buffer for a BCS I Biowaiver.
The Dissolution testing apparatus used in this evaluation
139 INDIA A
should conform to the requirements of the Dissolution
Guideline 2.0
A minimum of 12 dosage units of a drug product should be
141 INDIA A
evaluated to support the biowaiver request.
3.2.R.3 CERTIFICATE(s) OF SUITABILITY CEP

The declaration of access for the named FPP manufacturer
179 SOUTH AFRICA B
must be completed
A written commitment should be included that the applicant
180 SOUTH AFRICA B
will inform SAHPRA and the FPP manufacturer in the event of
changes or withdrawal.
The written commitment by the applicant should also
181 SOUTH AFRICA B
acknowledge that the withdrawal of the CEP would require a
full module 3.2.S to support the product dossier
The written commitment should accompany the copy of the
182 SOUTH AFRICA B
CEP.
Section 3.2.S.1.3 Should be assessed for completeness using
185 SOUTH AFRICA B
the checklist for 3.2.S.1.3
3.2.S.3.1 Elucidation of structure and other characteristics –
186 SOUTH AFRICA B
study is to identify polymorphs (exception: where the CEP
specifies a polymorphic form) and particle size distribution,
where applicable as per guidance in the section.
3.2.S.5 Reference standards or materials – information on the
191 SOUTH AFRICA B
SPP manufacturer’s reference standards.
3.2.S.7 Stability data must be provided, except where the
193 SOUTH AFRICA B
CEP specifies a re-test period that is the same as or longer
duration and storage conditions which are the same or higher
temperature and humidity as proposed by the applicant.
Stability data if required should be generated according to the
194 INDIA B
stability guideline should be submitted in 3.2.S.7
The Quality Overall summary 2.3 must be include a summary
196 INDIA B
of the additional data provided by the FPP
manufacturer/applicant.
3.2.R.7 PRODUCTION DOCUMENTATION

Copy of the batch manufacturing record including the
226 INDIA B
ingredient analytical reports, in process control test reports,
immediate product test reports, reconciliation records and a
certificate of analysis for the batch must be presented. For
minor changes, annual notifications will suffice
3.2.R.7.1 EXECUTED PRODUCTION DOCUMENTATION
Copies of the executed production documents should be
228 INDIA B
provided for the batch is used in the comparative the file
availability or by your waiver studies. Any notations made by
operators on the executed production documents should be
clearly legible.
For solid oral dosage forms, the biobatch should, at a
229 INDIA B
minimum, one-tenth that of full production scale or 100,000
tablets or capsules, whichever is the larger.
3.2.R.7.2 MASTER PRODUCTION DOCUMENTATION
Copies of the FPP master production documents should be
233 INDIA B
provided for each propose strength, commercial batch size
and manufacturing site.
The master production documents should include the master
234 INDIA B
formula
The master production documents should include the
235 INDIA B
dispensing, processing and packaging sections with relevant
material and operational details
The master production documents should include the relevant
236 INDIA B
calculations (e.g., if the amount of API is adjusted based on
the assay results or on the anhydrous basis)
237 INDIA B
identification of all equipment by, at minimum, type and
working capacity (including make, model and equipment
number, where possible)
The master production documents should include the process
238 INDIA B
parameters (e.g., mixing time, mixing speed, milling screen
size, processing temperature range, granulation end-point,
tablet machine speed (expressed as target and range)
The master production document should include the list of in-
239 INDIA B
process testing (e.g., appearance, pH, assay, blend
uniformity, viscosity, particle size, distribution, LOD (loss on
drying), weight variation, hardness, disintegration time, weight
gain during coating, leaker test, minimum fill, clarity, filter
integrity checks) and specifications;
240 INDIA B
precautions necessary to ensure product quality (e.g.,
temperature and humidity control, maximum holding time)
For sterile products, the master production documents should
241 INDIA B
include the reference SOPs in appropriate sections and a list
of all relevant SOPs at the end of the document.
The master production documents should include theoretical
242 INDIA B
and actual yield;
The master production documents should include Compliance
243 INDIA B
with GMP requirements
THE MASTER PRODUCTION DOCUMENTS SHOULD INCLUDE THE SAMPLING PLAN
SHOWING THE FOLLOWING:
Steps where sampling should be done (e.g., drying,
244 INDIA B
lubrication, compression) are clearly stated
Number of samples that should be tested are clearly stated
245 INDIA B
open brackets (for blend uniformity testing of low doss FPPs,
blend drawn using a sampling thief from X positions in the
blender),
Frequency of testing is clearly stated (e.g., weight variation
246 INDIA B
every x minutes during compression or capsule filling)
3.2.R.8 OTHER
The PDF version of the SCoRE document should be included
247 SOUTH AFRICA B
in this Module in the eCTD (TBC) submission
And additional MS Word version of SCoRE should be
248 SOUTH AFRICA B
included in the working documents folder
The font used in the main text should be Arial, size 11
249 SOUTH AFRICA B
The SCoRE document should be revised and submitted with
250 SOUTH AFRICA B
the change history each time additional data is provided
during the assessment process.
For variations, the SCoRE document should be completed in
251 SOUTH AFRICA B
its entirety (regardless of the proposed change), it should be
included information on all strengths, with any changes
highlighted in yellow and it should be provided at the time of
filing
For the APIF, if information is in the closed part of the DMF,
252 SOUTH AFRICA B
reference to the closed part should be made (where
applicable)
All blue text (guides and examples) should be deleted when
253 SOUTH AFRICA B
submitting the SCoRE document
The titles and the numbering style must not be changed or
254 SOUTH AFRICA B
deleted (add “not applicable closed “if necessary)
3.3 REFERENCES
Copies of any articles (journal/reference books) referenced in
255 SOUTH AFRICA B
support of any statement made in module 3 should be
included in the section.

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Module: 1.

0 Due diligence Report

No. Deficiency Statement Accountability Priority

SAHPRA’s RECOGNISED REGULATORY AUTHORITIES

33 European Medicines Agency Centralised Procedure (EMA SOUTH AFRICA B

34 European Medicines Agency Decentralised Procedure (EMA SOUTH AFRICA B

35 Health Canada SOUTH AFRICA B

36 Medicines and Health Products Regulatory Agency (MHRA), SOUTH AFRICA B

37 Ministry of Health, Labour and Welfare (MHLW), Japan SOUTH AFRICA B

38 Swiss Agency for Therapeutic Products (Swissmedic) SOUTH AFRICA B

39 Therapeutic Goods Administration (TGA), Australia SOUTH AFRICA B

40 US Food and Drug Administration (US FDA) SOUTH AFRICA B

1.0 LETTER OF APPLICATION

137 The letter should include Sequence number SOUTH AFRICA B

MANUFACTURING, PACKAGING AND TEST SITES

188 The license number should be provided INDIA B

189 The date of issue of the license should be provided INDIA B

DECLARATION AND SIGNATURE

215 The application should be dated SOUTH AFRICA B

No. Deficiency Statement Accountability Priority

1.3.1.1 PI (PROFESSIONAL INFORMATION)

Confirmation should be included to confirm that the printed PI

5 It should be confirmed that the language, spelling and SOUTH AFRICA B

7 Each page of the PI should be initialled by the pharmacist SOUTH AFRICA B

HEADING TO BE USED ACCORDING TO GUIDELINE 2.6

94 In the case of a medicine for oral administration which SOUTH AFRICA B

106 A visual description of appearance of the product (colour, SOUTH AFRICA B

123 Advice of preventative measures to avoid certain adverse SOUTH AFRICA B

146 The statement X is contraindicated in children aged x to SOUTH AFRICA B

y><years, months> <or any other relevant subsets e.g.

155 The patient populations/special populations not studied in SOUTH AFRICA B

156 Patients populations/special populations excluded from SOUTH AFRICA B

160 A contraindication in the paediatric population should be listed SOUTH AFRICA B

161 Porphyria, if absolutely contraindicated should be listed. SOUTH AFRICA B

4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE

167 Serious adverse reaction to which healthcare professionals SOUTH AFRICA B

174 Any particular risk associated in incorrect route of SOUTH AFRICA B

4.5 INTERACTION WITH OTHER MEDICINES AND OTHER FORMS OF INTERACTION

187 Interactions referred to in other sections of the PI should be SOUTH AFRICA B

188 Additional information on special populations should be SOUTH AFRICA B

189 Information specific to paediatric population SOUTH AFRICA B

193 Pregnancy non-clinical data SOUTH AFRICA B

4.8 UNDERSIABALE EFFECTS

a) DESCRIPTION OF SELECTED ADVERSE REACTIONS

211 Information on a specific ADR which may be useful to SOUTH AFRICA B

213 Special populations should be included SOUTH AFRICA B

220 Information specifically observed in special populations such SOUTH AFRICA B

222 Special mention should be made of those medicine/strength SOUTH AFRICA B

5.2 PHARMACOKINETIC PROPERTIES

238 Biotransformation: degree of metabolism; which metabolite; INDIA A

239 Elimination: elimination half-lives, total clearance; enter and/or INDIA A

relative portion of the hepatic and renal elimination fraction,

240 Linearity/nonlinearity: linearity/non-linearity of INDIA A

241 Relationship between dose/concentration/pharmacokinetic INDIA A

5.3 PRE-CLINICAL SAFETY DATA

245 Environmental risk assessment (ERA) to be included only SOUTH AFRICA B

260 The storage instructions should indicate storage SOUTH AFRICA B

265 Recommended temperature range and maximum duration of SOUTH AFRICA B

6.6 SPECIAL PRECAUTIONS FOR DISPOSAL OF THE USED MEDICINE OR WASTE

288 A cross-reference in section 4.2 to the relevant information in SOUTH AFRICA B

291 Information on risks due to occupational exposure should be SOUTH AFRICA B

No. Deficiency Statement Accountability Priority

1.3.1.2 STANDARD REFERENCE MULTISOURCE MEDICINES

307 SAHPRA monograph for “old medicines” SOUTH AFRICA B