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We know bioequivalence studies are generally performed on the highest strength of a product.
When can a Bioequivalence study be performed on a lower strength where the applied product has multiple strengths?
@FRD
You should consider at least below physicochemical properties of API:
– Solubility of API
– pKa, LogP value of API
– Absorption site of APISome of the essential topics you should covered in your pharmacy study program:
– pharmacy and the law,
– pharmacology,
– physiology and pharmaceuticals,
– Biopharmaceutics,
– pharmaceutical management and pharmacotherapy etc.- This reply was modified 1 year, 4 months ago by .
@Pharma
I got this helpful- https://www.pharmaspecialists.com/p/available-bcs-classification-of-drugs.html- This reply was modified 1 year, 6 months ago by .
- This reply was modified 1 year, 6 months ago by .
Basic GMP requirements for new pharma manufacturing facility:
– Appropriate design and location,
– Proper resources: personnel, buildings, equipment, materials,
– Clearly defined and systematically reviewed processes,
– Trained personnel,
– Proper storage and distribution procedure,
– Internal and external health and safety,
– Appropriate waste disposal system etc.Reference: https://www.pharmaspecialists.com/2022/03/gmp-facility-design-gmp-golden-rules.html
A biowaiver is applicable when the drug substance(s) in test and reference products (RLD) are
identical.BCS-based biowaivers are applicable to drug products where the drug substance or substances exhibit high solubility and, either high permeability (BCS Class I) or low permeability (BCS Class III).
In order for a drug product to qualify for a BCS-based biowaiver, criteria with respect to the composition (excipients) and in vitro dissolution performance of the drug product should be satisfied.
Ideally, the composition of the test product should mimic that of the reference product. However, where excipient differences exist, they should be assessed for their potential to affect in vivo absorption. This should include consideration of the drug substance properties as well as excipient effects.
When applying the BCS based biowaiver approach, comparative in vitro dissolution tests should be conducted using one batch representative of the proposed commercial manufacturing process for the test product relative to the reference product. The test product should originate from a batch of at least 1/10 of production scale or 100,000 units, whichever is greater, unless otherwise justified.
To qualify for a BCS-based biowaiver for BCS Class I drug substances, both the test product and reference product should display either very rapid (≥85% for the mean percent dissolved in ≤ 15 minutes) in vitro dissolution characteristics, or rapid (≥85% for the mean percent dissolved in ≤ 30 minutes) and similar in vitro dissolution characteristics (i.e., based on f2 comparison), under all of the defined conditions as below:
– Apparatus: paddle or basket.
– Volume of dissolution medium: 900 mL or less (it is recommended to use the volume selected for the quality control (QC) test).
– Temperature of the dissolution medium: 37±1°C.
– Agitation: for paddle apparatus – 50 revolutions per minute (rpm)and for basket apparatus – 100 rpm.
– At least 12 units of reference and test product should be used for each dissolution profile determination.
– Three buffers: pH 1.2, pH 4.5, and pH 6.8. Pharmacopoeial buffers should be employed. Additional investigation may be required at the pH of minimum solubility (if different from the buffers above).
– Organic solvents are not acceptable, and no surfactants should be added.
– Samples should be filtered during collection, unless in situ detection methods are used.
– For gelatin capsules or tablets with gelatin coatings where cross-linking has been demonstrated, the use of enzymes may be acceptable, if appropriately justified.Two dissolution profiles are considered similar when the f2 value is ≥50. When both test and reference products demonstrate that ≥85% of the labeled amount of the drug is dissolved in 15 minutes, comparison with an f2 test is unnecessary, and the dissolution profiles are considered similar. When the coefficient of variation is too high, f2 calculation is considered inaccurate and a conclusion on similarity in dissolution cannot be made.
Reference: M9 Biopharmaceutics Classification System Based Biowaivers
Hi Ashiqur!
Here is the top 10 check points for facing EU GMP audit:1. Job Training
2. Quality Policy
3. Good Housekeeping Program
4. Equipment Qualification and Calibration Program
5. Cleaning Validation
6. Test specification and control
7. Inventory and Vendor Control Program
8. Process Validation Program
9. Reprocessing/ Reworking Procedure
10. Complaint Handling and Customer Satisfaction ProgramThe above list is not complete but will be important for audit preparation.
Shelf temperature and chamber pressure are to be considered as critical process parameters for lyophilization.
It’s depend on molecule nature, dosage form, patient availability etc.
But there are stringent requirements for a generic drug to be claimed bioequivalent to a reference product. One requirement is that the bioavailability of the generic product should be closely similar to that of the reference product.
Following regulatory authorities also highly stringent:
UK MHRA
Swissmedic
SFDA
Danish Medicines Agency
Norwegian Medicines AgencyThe revised Guideline addresses what constitutes formality in QRM and it outlines how varying degrees of formality may be applied during QRM activities, including when making risk-based decisions.
