weeks 1-3 Flashcards
Target product profile
- Defines the minimal/ideal profile marketed product
- shows ultimate goals of the proposed therapy development effort i.e. disease indication, patient population, delivery mode, treatment regimen and standards of clinical efficacy.
sections of the TPA not contained in the the FDA document that the sponsor might want to consider
- primary markets
- pharmacoecenomics
- cost of goods
- target price
- current gold standard
- possible market extensions
Efficacy component of TPP
Efficacy: Drives PK/PD attributes of the candidate via stipulation of a magnitude and duration of effect; drives evaluation of alternative molecular and formation strategies.
Safety component of TPP
drives side effect profile, what is tolerated and what is not
Toxicity in some cases
Quality component of a TTP
- defines shelf life(dictated in part by formulation)
- packaging (diff. grades vs shelf life cost)
- quality testing components
- need for particular excipients
NDA
the vehicle through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing
Required information for the summary of the NDA
- proposed text of the labelling, support for the inclusion of each statement on the labelling
- identify the pharmacologic class of the drug, intended use and the potential therapeutic benefits
- CMC
- Non clinical pharmacology and toxicology
- human pharmacokinetics and bioavailibility section
- clinical data
- post marketing
Composition of drug product
-Drug substance + dosage form
Factors influencing dose form
Physicochemical/biopharmaceutical properties of the drug,
- chemical and physical stability
- metabolic processe
- cultural and personal preferences
Solid state aspects
Different solid state forms; polymorphs, salts and amorphous forms
- Tests = XRD, Raman Microscopy
Biopharmaceutical classification system
1) high solubility High permeability
2) low solubility, high permeability
3) High solubility, low permeability
IV) Low solubility, Low permeability
Limiting factors of bioavailability
- Lipinski values outside the rule of 5 (remember there are only 4 rules)
- phsyiological facotrs (metabolism and efflux)
specifications
A set of tests and limits which are applied to the product in order to ensure that every batch is of satisfactory and consistent quality throughout its shelf life
- should also describe the label, container etc
- cannot be altered without generating a new specification with a different specification number (coz its a new product)
Internal uses of the specification
- describes the product
- QC, is it okay for market
- Batch testing
- internal dossier of important info
- API sourcing/manufacturing
- Regulatory affairs
- Technical development
- Familiarity training purposes
External uses of the specification
- Submission for reg. approval
- Basis for the certificate of Assurance/ Batch record
- Pseudo product information
Product spec vs batch record
- Batch record shows values obtained from tests, indicates if the criteria was met
- has the batch number
Format of product spec
- Date
- author
- approver
- company name
- document number
- name of product
- pack size
Body: physical description and container description
- active ingredients with limits and test methods
- excipients
- tests
Pharmacopoeia
- exist to provide standards ensuring the quality of medicines
- provide controlled standardised tests, analytical methods and acceptance criteria for establishing the quality of: API, Excipients. formulated product
Medicinal substance monograph
Defines the API i.e. Acetyl Salicylic acid
1: introductory(structure, CAS number, preparations etc)
2: Identification (methods A +B)
3: tests i.e. appearance on solution, Heavy metals, loss on drying. Related substances
4: assays, how much is there
General monographs
Specific to the dose form: provides guidance for determining the quality of medicines prepared from said dose form
- Definition
- production
- tests
- storage
Specific monographs
For complete finished products, basically medicinal and general monographs combined
Appendices
Standard solutions Buffers Analytical Methods Detail of the Test methods eg dissolution Detailed Test Apparatus
