Mr. Vivek P. Chavda, Dr. Moinuddin M. Soniwala
Department of Pharmaceutics, B.K. Mody Government Pharmacy College,
Rajkot – 360003, Gujarat (India)
In recent years, many important initiatives have been undertaken by regulatory authorities and industry associations to promote international harmonization of regulatory requirements. International Conference on the Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) was organized in April 1990 and has as its sole and primary purpose the creation of international standards for the purpose of pharmaceutical research. This process was initiated in order to harmonize the submission requirements for new pharmaceuticals in the three main regions of Europe, the United States, and Japan and to avoid duplication, inefficiencies and delays.
The six cosponsors of ICH were
- European Commission,
- European Federation of Pharmaceutical Industry Association (EFPIA),
- Japanese Ministry of Health (MHW),
- Japanese Pharmaceutical Manufacturers Association (JPMA),
- Food and Drug Association (FDA), and the Pharmaceutical Research
- Manufacturers of America (PhRMA)
Reference ID: PHARMATUTOR-ART-1950
The ICH Steering Committee includes representatives from each of the ICH sponsors and the IFPMA, as well as observers from the World Health Organization, the Canadian Health Protection Branch, and the European Free Trade Area. In the Federal Register of March 7, 1996 (61 FR 9310), FDA published a draft tripartite guideline entitled ‘‘Guideline for the Photostability Testing of New Drug Substances and Products.’’ The notice gave interested persons an opportunity to submit comments by June 5, 1996.
After consideration of the comments received and revisions to the guideline, a final draft of the guideline was submitted to the ICH Steering Committee and endorsed by the three participating regulatory agencies at the ICH meeting held on November 5, 1996. In the Federal Register of September 22, 1994 (59 FR 48754), the agency published a guideline entitled ‘‘Stability Testing of New Drug Substances and Products.’’ The guideline addresses the generation of stability information for submission to FDA in new drug applications for new molecular entities and associated drug products. In the discussion of ‘‘stress testing’’ for both drug substances and drug products, the guideline states that ‘‘light testing’’ should be an integral part of stress testing and will be considered in a separate ICH document.
Prior to 1960s there were not many controls over introduction of new drugs and also over the assurance of the quality by the manufacturer over his established drug products. Around 1970s the pharmaceutical industry started getting global but the registration of medicines remained a national responsibility.Although the laws of all the countries were based on the same fundamental obligations to evaluate the quality, safety and efficacy the detailed technical requirements differed from country to country. So the companies had to duplicate many time consuming and expensive test procedures, in order to market new products, internationally. All this resulted in unnecessary expenses and long delays in introducing new drugs. Hence a necessity to harmonize or make uniform, the testing procedures and regulatory requirements of different countries was felt and the result is the birth of ICH in April 1990.
The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is a unique project that brings together the regulatory authorities of Europe, Japan and the United States and experts from the pharmaceutical industry in the three regions to discuss scientific and technical aspects of product registration.
Objectives of ICH
- More economical use of human, animal, and material resources.
- Elimination of unnecessary delay in the global development & availability of new medicines.
- Maintaining safeguards on Quality, safety & efficacy, and regulatory obligations to protect public health.
The ICH topics are divided into four categories and ICH topic codes are assigned according to these categories
1. QUALITY GUIDELINE
Those relating to chemical and pharmaceutical Quality Assurance (Stability Testing, Impurity Testing, etc.)
2. SAFETY GUIDELINE
Those relating to in vitro and in vivo pre-clinical studies (Carcinogenicity Testing, Genotoxicity Testing, etc.)
3. EFFICACY GUIDELINE
Those relating to clinical studies in human subject (Dose Response Studies, Good Clinical Practices, etc.)
4. MULTIDICIPLINARY GUIDLINE
Cross-cutting Topics which do not fit uniquely into one of the above categories (MedDRA, ESTRI, M3, CTD, M5)
Q1A (R2): Stability testing of new drug substances and products.(Revised guideline)
Q1C: Stability testing of new dosage forms.
Q1D: Bracketing & Matrixing designs for stability testing of new drugs substances and products.
Q1E: Evaluation of Stability data.
Q1F: Stability Data Package for Registration Applications in Climatic Zones III and IV
“PHOTOSTABILITY TESTING OF NEW DRUG SUBSTANCES AND DRUG PRODUCTS"
B. LIGHT SOURCES
C. PROCEDURE (DECISION FLOW CHART)
2. DRUG SUBSTANCES
A. PRESENTATION OF SAMPLES
B. ANALYSIS OF SAMPLES
C. JUDGEMENT OF RESULTS
3. DRUG PRODUCTS
A. PRESENTATION OF SAMPLES
B. ANALYSIS OF SAMPLES
C. JUDGEMENT OF RESULTS
A. QUININE CHEMICAL ACTINOMETRY
This document is an annex to the ICH parent stability guideline and addresses the recommendations on what should be submitted regarding stability of new dosage forms. The light testing is an integral part of the stress testing.
NEW DOSAGE FORMS
Stability protocols for new dosage forms should follow the guidance in the parent stability guideline. However, a reduced stability database at submission time (e.g., 6 months accelerated and 6 months long term data from ongoing studies) may be acceptable in certain justified cases.
The intrinsic photostability characteristics of new drug substances and products should be evaluated to demonstrate that, as appropriate, light exposure does not result in unacceptable change.The guideline does not cover the photostability of drugs after administration.Normally, photostability testing is carried out on a single batch of material selected as described under Selection of Batches in the Parent Guideline. Under some circumstances these studies should be repeated if certain variations and changes are made to the product (e.g., formulation, packaging).
Example4: Nifedipine (NIF) a 1, 4-dihydropyridine calcium channel antagonist, undergoes photodegradation to nitroso analogues of dihydronifedipine (NDNIF) when exposed to sunlight. Photodegradation products of NIF have no clinical activity, so different formulations of NIF must remain unchanged. If NIF preparations become unstable in exposure to light, they could cause therapeutic failure. The present study was carried out in order to investigate the photostability of commercially available NIF products.
A systematic approach to photostability testing is recommended covering, as appropriate, studies such as:
 Tests on the drug substance;
 Tests on the exposed drug product outside of the immediate pack; and if necessary;
 Tests on the drug product in the immediate pack; and if necessary ;
 Tests on the drug product in the marketing pack.
WAYS FOR STABILIZATION5: Suitable packing Photo stabilizer (Light absorber) Protection of drug from light during mfg. Coating. Eg. Photo stabilization of Molsidomine Tablet;Molsidomine Morpholine dvt. (Potential carcinogenic) It was stabilized by;
* Incorporation of light absorbing excipients. colorants – curcumine and azorubine
* Incorporation of pigments. (eg. TiO2 and ZnO3)
* By coating a) white coating ( 4.8% TiO2)
b) colored coating ( yellow & red iron oxide added to std. coating containing 4.8%TiO2)
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