Applicant/PHCR:Product proprietary name:Dosage form and strength

MRF2

MEDICINES CONTROL COUNCIL

APPLICATION FOR REGISTRATION OF A MEDICINE
SCREENING FORM

Where appropriate, abbreviations Y, N, or N/A should be used. Questions may not be deleted and numbering may not be changed. The comment section may be used for any additional information or explanation.

The application should be completed fully and accurately and presented in the prescribed format. Each item must be referenced to the relevant page number of the application, if applicable.

Note that the requirements of the Trade Metrology Act with regard to the use of the metric system should be complied with.

Applications that are incomplete or are non-compliant in any way will be returned as non-compliant.

Applicant/Prospective Holder of the Certificate of Registration (PHCR):
Product Name: / Date of Submission:
APIs:
Type of application
1.1Indicate the type of medicine and the type of data included as proof of efficacy using a check mark () or a cross (X):
Human Medicine:_____NCE_____Pre-clinical
____Pharmaceutical_____Multisource_____Clinical
____Biological_____Biosimilar_____Biostudy
Veterinary Medicine:_____Line extension_____Other
____Pharmaceutical_____Call-up
____Biological
1.2Review procedure:
______Routine______AMRP______Expedited (Fast Track Application)
GENERAL ADMINISTRATIVE INFORMATION / Y, N N/A / Page / MRA use
2.1If Expedited review (Fast Tracking) has been approved, is a copy of the approval letter attached to the screening form?
2.2If the Abbreviated Medicines Review Process (AMRP) has been approved, have expert reports on chemical-pharmaceutical, pharmaco-toxicological and clinical documentation been included.
2.3Is the application in the format prescribed by MRF1? (including headers)
2.4If the application is submitted in the EU /CTD format, is a separate document cross-referencing the MRF1 format to the EU/CTD format included?
2.5Is a request for exemption with full motivation included for PARTs not being addressed?
2.6Are all photocopies clearly legible?
PART 1AADMINISTRATIVE PARTICULARS / Y, N N/A / Page /
MRA use
3.1Are the full particulars of the PHCR included in PART 1A?
(i.e. name, business and postal addresses, telephone, fax, e-mail)
3.2Is the application signed by the authorised person and/or a pharmacist (if the responsible/authorised person is not a pharmacist)? (see 5.7)
3.3Is the letter of authorisation for communication on behalf of the PHCR included in the application (signed by the person responsible for the overall management and control of the business)?
PARTs 1C and 1DLABELLING and FOREIGN REGISTRATION
4Labelling and foreign registration / Y, N N/A / Page /
MRA use
4.1Is the product registered in any other country?
4.2Is proof of registration of the product in other countries included in PART 1D?
4.3Is a copy (or copies) of the latest version of the package insert approved by the regulatory authorities in PART 1D included?
4.4Has the product been rejected for registration by any regulatory authority?
4.5If yes to 4.4 above, was rejection due to
a)safetyb)efficacy
c)safety and efficacyd)other reason (specify):
………………………………………………………………………………………
4.6Is the proposed package insert included in PART 1C?
4.7Is an electronic copy of the package insert also included on diskette or CD in MS Word?
4.8Is the informationin the package insert cross-referenced to supporting evidence in a)PART 5 and/or
b)the latest edition of the standard reference books? /
a
b
4.9Are all the references referred to in the package insert included?
4.10Is the package insert typed in double spacing in black print?
4.11Does the package insert comply with Regulation 9?
4.12Is the proposed patient information leaflet (PIL) included in PART 1C?
4.13Is an electronic copy of the PIL also included (diskette or CD in MS Word)?
4.14Is the informationin the PIL cross-referenced to the package insert?
4.15Is the PIL typed in double spacing in black print?
4.16Does the PIL comply with Regulation 10?
4.17Are pre-clinical data submitted in PART 4?
4.18Are clinical data submitted in PART 5?
4.19Are residue depletion data and withdrawal time for veterinary medicines in food-producing animals submitted in PART 5?
4.20Are the Clinical studies indexed and numbered?
4.21Have all raw data (individual patient data) been removed?
4.22Is either a Clinical Overview / Clinical Expert Report (CER) or an SBRA submitted?
4.23Are the tables and graphs in the CER cross-referenced to the documentation submitted?
5INSPECTORATE
/
Y, N N/A
/
Page/ Annex
/
MRA use
5.1Does the label information comply with Regulation 8?
5.2Isa)a copy of the latest inspection report (not older than 3 years) or
b)an equivalent document,
from the Medicines Regulatory Authority of the country of manufacture of imported products available for inspection? / a
b
5.3Isa)a copy of the latest GMP certificate (not older than three years) or
b)a copy of the appropriate manufacturing licence attached)? / a
b
5.4Isa)a Certificate of a Pharmaceutical Product (CPP) in terms of the WHO certification scheme (Free Sales Certificate), and / or
b)a copy of the registration or marketing authorisation certificate for the product, included? / a
b
5.5Is proof (copy of the certificate) of registration in terms of Act 53 (Pharmacy Act) of the Applicant/PHCR as a) a pharmacy or
(read with guidelines)b)a pharmacist included? /
a
b
5.6Is proof of registration (copy of the certificate) of the Responsible Pharmacist in terms of Act 53 (Pharmacy Act) included?
5.7Is proof of registration (copy of certificate) of the pharmacist who signed the dossier, if not the Responsible Pharmacist, in terms of Act 53 included?
5.8Is the batch manufacturing record of the sample
a) included in PART 3E, or
b) available for inspection? / a
b
5.9Is the CoA for the sample included?
5.10Is Master documentation for PART 3Ea) included, or
b) available for inspection? / a
b
5.11Is a permit to manufacture specified Schedule 5 or 6 products included?
5.12HCR, MANUFACTURING, TESTING, PACKAGING, FPRC, FPRR
5.12.1If more than one site is involved, is the site for each stage clearly identified and the complete physical address of each reflected in PART 3E?
5.12.2Pleaseprovide the following details:
Licence no & date of issue / SMF no and date of submission & / Date of last inspection / Local or Foreign? / GMP Status / Contract with HCR/PHCR
in place? / Inspection flow diagram of manufactured products included?
HCR
Manufacturer
1
2
Packer
1
2
Testing Lab
1
2
6PART 2AApplications with biostudy or other data as proof of efficacy(other than clinical) / Y, N N/A / Page /
MCC use
Please check page numbers referred to for correctness
6.1Is proof of (safety &) efficacy based on a) bioequivalence study (in vivo) or b) in vitro data only. / a
b
6.2If proof of safety and efficacy is indicated as N/A has a motivation for exemption been submitted?
6.3Are all the components of the biostudy submitted including:
aDate and place of study
bThe Protocol
cEvidence of ethical approval
dAssay data validation plus representative chromatograms
eInvestigators' curriculum vitae
fMonitor's / Quality Assurance statement
gAuditor's certificate / statement? / a
b
c
d
e
f
g / a
b
c
d
e
f
g / a
b
c
d
e
f
g

6.4Do the product results meet the acceptance criteria for Cmax and AUC as prescribed in the guidelines?

6.5Was the biostudy performed using the innovator product currently registered and procured in South Africa?

6.6If not, isa)a full report on comparative data to demonstrate equivalence of the reference product to the S.A. registered innovator product submitted?b)the country of procurement of the reference product and name and address of the applicant stated?c)country of procurement, country with which MCC aligns itself?

/ a
b
c

6.7If a biowaiver is requested for different strengths of the product:

a)are the different strengths proportionally formulated?

b)are full details of each formulation strength included with this application in PART 2A?

c)were the different strengths manufactured by the same manufacturer, at the same site, with API(s) sourced from the same manufacturer?Include a statement in PART 2A.

d)Have appropriate quantitative methods e.g. dissolution data in three media in accordance with the Dissolution guideline been used to confirm similarity and

is a report with the appropriate data included with this application [e.g. similarity (f2) factor]?

6.8If a BCS biowaiver is requested, are

a)a motivation and justification

b)with supporting data and

c)a full report included, e.g.comparative dissolution data comparing the test and reference products in three dissolution media, pH's 1,2; 4,5 and 6,8?

/ a
b
c

7PART 3PHARMACEUTICAL & ANALYTICAL

/ Y, N N/A / Page / MRA use
7.1Is the appearance of the sample comparable to the description given under identification in the package insert?
7.2Is a facsimile of the label included in PART 1C?
7.3Is the solubility of the API(s) in water and in the solvent relevant to the formulation quantified in PART 3A? (refer to P&A Guideline)
7.4Is the APIF or open part of the DMF (plasma master file for a biological) clearly indexed?
7.5Are Certificates of Analysis (CoAs) for the API(s) included in PART 3A?
7.6Is the method(s) of synthesis of the API(s) included?
7.7Are stability data submitted in PART 3A for the API(s) in compliance with the Stability guideline?
i)NCEs : Environmental test conditions (Temperature and humidity)
  • Real time conditions
  • Accelerated conditions
Stability data submitted
  • Real time data (weeks/months /years)
  • Accelerated data (weeks/months/years)
Stability Batches
  • Number and types/sizes (production, pilot or experimental) of batches
ii)Well known entities: a)supporting literature or
b)stability data / a
b
7.8Where more than one manufacturer of the API (not the same parent company) is used, are comparative chemical and physical data in tabular format included to demonstrate equivalence?
7.9Has the comparative chemical and physical data been generated by the same testing laboratory (laboratory stated) under the same conditions?
7.10Where more than one site of the same parent company is used and an identical method of synthesis is used at these sites:
(a)has a statement to this effect been included?
(b)have valid CoAs issued by each site for at least two batches within the retest period at the time of submission of the application been included? /
a
b
7.11Do all the ingredients in the unit formulation in PART 3B correspond with those in the batch formulation in PART 3E?
7.12Are reasons stated for overages of the quantity of the active pharmaceutical ingredient(s) (APIs) and/or other ingredients in PART 3B?
7.13Is the potency calculation and/or equivalency equation included for the API(s) in PART 3B?
7.14Is the composition of combinations/mixtures in formulations e.g. pH adjusters, coating mixtures, capsule shells, stated separately?
7.15Are specifications and control procedures for all ingredients listed in PART3B included in PART 3C?
7.16Is the frequency of testing of water stated in PART 3C? (read with P&A Guidelines)
7.17Are container specifications & control procedures included in PART 3D?
7.18Are tests performed by the supplier of the containers clearly indicated in PART3D?
7.19Are tests performed by the manufacturer of the final product on the container components, clearly indicated in PART3D?
7.20Are the batch manufacturing formulations & batch sizes included in PART3E?
7.21Is a)a comprehensive flow diagram, or
b)a comprehensive description
of the manufacturing process, detailing the various production stages, equipment types & sizes, sieve sizes, machine settings, duration of treatment, temperature, humidity, light, in-process controls and other relevant information included? / a
b
7.22Is a description of the Packaging procedure and the conditions and stages of packaging for specific dosage forms included in PART 3E?
7.23Is a manufacturing validation protocol or report included in PART 3E? (If a VP is included a VR should be submitted only when requested by the inspectorate.)
7.24Are specifications and control procedures for the final product submitted in PART 3F?
7.25Is assay method validation data submitted in PART 3F?
7.26Are all the analytical and non-analytical release criteria and tests indicated in PART 3F?
7.27a)Are stability data submitted in PART 3G in compliance with the Stability guideline?
b)Is a tabulated summary of the batches, i.e. sizes, numbers, type, packaging material, and conditions and period of testing included for each manufacturer? / a
b
7.28Are details of the container, batch number, batch size, date of manufacture of the batch, and storage conditions reflected in PART 3Gb)?
7.29Are all the stability specification parameters listed in PART 3F included in the stability data presented in PART 3G?
7.30a)Have stability data been derived with API sourced from the manufacturer identified in PART 3A? / a
b)If not, are pharmaceutical equivalence data of the API sources included? / b
7.31Have stability data been derived from the product packed in packaging material detailed in PART 3D?
7.32Is validation data for the stability testing assay method (if pharmacopoeial and/or different to that in PART 3F) included?
7.33Isa)the pharmaceutical development submitted in PART 3H or
b)a Pharmaceutical Expert Report submitted in PART 2C? / a
b
7.34Are details of expertise and the premises used in PART 3I included?

Comment or explanation

Item number / Comment or explanation / Page number

UPDATE HISTORY

Date / Reason for update / Version & publication
June 2006 / Restructuring and changes including industry comments / Jun06 v2 July 2006
Date for implementation / 20 July 2006
June 2007 / Amendment of 1.1, Screening outcome; addition of 2.2 / Jun07 v2 June 2007
Date for implementation / 2 July 2007
SCREENING OUTCOME for official use only
Application no.:
Ops & Admin / Date:
Accept / Hold / Return
MER / Date:
Accept / Hold / Return
Clinical / Date:
Accept / Hold / Return
Inspectorate / Date:
Accept / Hold / Return

Registration of MedicinesMRF2 Screening form

6.02 MRF2 Jun07 v3.docJune 2007Page 1 of 8