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Prequalification of Medicines Programme QSM / EMP / HSS
Documentation
1. The product submitted for prequalification is NOT in the latest EOI (should be the same API and strength)
2. The cover letter from the applicant did not clearly indicate that the information submitted is true and correct. 3. The PQIF and BTIF are NOT submitted or submitted but Not in word document.
4. The dossier submitted does NOT have (clear) table of contents and the numbering of dossier pages does not follow one sequence.
5. The FPP applicant has made reference to the APIMF, but a copy of the Letter of Access from the APIMF holder is not submitted.
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Common Deficiencies
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Quantitatively (over the physiological pH range 1.26.8)* For a low-solubility API, particle size, polymorphism, should be characterized
(based on the lot used in clinical or bioequivalence studies)
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S.2 Manufacture
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S.3 Characterisation
Discussion on potential impurities is not sufficient
The following information should be provided: List of impurities including chemical name, structure, and origin (e.g., starting materials, by-products, intermediates, chiral impurities, degradations) All potential residual solvents should be discussed, and controlled in specifications unless adequately justified. If catalysts are used in the synthesis, these should be controlled in specifications unless adequate justified Data on observed impurities in batches used in clinical or BE study
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S.4
The suitability of the monograph method to determine new impurities due to a new route of synthesis must be demonstrated. If not, propose a new validated method and a qualified limit.
The purity and potency methods should be verified for specificity, precision and accuracy. The API specification from the manufacturer of the FPP should be provided, including the parameters related to the specific product. It should be dated and signed by authorized personnel.
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Identity of materials of construction of primary packaging Specifications for components in contact with the API should include a specific test (eg IR) for identity.
Container specifications should be provided by API packager, not the packaging supplier. The packaging should be food and/or pharmaceutical grade
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Common Deficiencies
(FPP)
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White to off white coloured capsule shaped biconvex uncoated tablets with central breakline on one side and debossed with A on other side
The primary packs are cylindrical, white, opaque, inductionsealed HDPE bottle fitted with a white Non CRC Screw Cap and containing 1 gm Silica gel bag and Rayon Sani coil.
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WHO prequalification programme: Training workshop March 2010, Beijing
The qualitative composition of mixtures, such as Opadry colourants, capsule shells, printing ink, is not provided.
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Lack of information on physico-chemical characteristics of the API which may have an impact on the manufacturing and performance of the product. such as particle size distribution, bulk/tapped density, polymorphic form
Compatibility of the API with excipients and in case of FDCs compatibility between APIs are not studied or at least not shown in the dossier.
Compatibility studies often report appearance only. Studies should include chromatographic results (potency and impurity). e.g. Rifampicin/Isoniazid
Rationale behind choice of manufacturing process, overages (if any), not given. e.g. Rifampicin
WHO prequalification programme: Training workshop March 2010, Beijing
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Comparison of dissolution properties of pivotal batches with future commercial batches, post-approval changes Setting of dissolution specification For solid dosage forms, it is a requirement to submit comparative dissolution data for the biobatch and innovator/comparator batch used in the bioequivalence. These data can be included in both part quality and bioequivalence study of the dossier.
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WHO prequalification programme: Training workshop March 2010, Beijing
Equipment should, at minimum, be identified by type (e.g., tumble blender, in-line homogeniser) and working capacity process parameters such as time, temperature, speed should be indicated
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WHO prequalification programme: Training workshop March 2010, Beijing
Confirmation/commitment that three consecutive, production-scale batches of this drug product will be subjected to prospective validation.
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WHO prequalification programme: Training workshop March 2010, Beijing
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If the tablet contains a score (justified), a one-time study of uniformity of tablet halves should be provided. refer to TABLETS,
Subdivision of tablets (EP, 5.5, p. 4166)
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Documentation in English
Original documents to be submitted with translation
Certificates, Manufacturing license, MA, GMP, TSE Manufacturing process documentation Batch manufacturing record Validation reports Specifications and CoAs
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Documentation in English
Terms of specification: essential to be correct. Example: IR/UV absorption chromatogram does not exist. it should be spectrum Moisture: is not equal to Water in a molecule with two moles of water of crystallization. It should be water content Calculated on dehydrated products is not an acceptable term for anhydrous basis. Tips: use pharmacopoeia Int Ph/USP/BP terms
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WHO prequalification programme: Training workshop March 2010, Beijing
Other sources of information: refer to the drug information of innorvators, approved generics for SmPC, FPP description, packaging information, etc. WHOPARs: http://healthtech.who.int/pq/WHOPAR/WHOPARPRODUCTS/WHO PAR_Index.htm EPARs: http://www.emea.europa.eu/htms/human/epar/a.htm
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Thank you
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