Stability Testing Photostability Testing of New Drug Substances and Products-Q1B.pptx

The ICH Guideline, Stability Testing Photostability Testing of New Drug Substances and Products-Q1B addresses the recommendations for photostability testing, an integral part of stress testing. This document is an annex to the Parent Guideline and focuses on evaluating the intrinsic photostability characteristics of new drug substances and products.

1. Stability Testing: Photostability Testing of New Drug Substances and Products Q1B The ICH Guideline addresses the recommendations for photostability testing, an integral part of stress testing. This document is an annex to the Parent Guideline and focuses on evaluating the intrinsic photostability characteristics of new drug substances and products. by Trishala Bhatt

2. General 1 Light Testing Light testing is an integral part of stress testing, and photostability testing is carried out on a single batch of material selected as described under Selection of Batches in the Parent Guideline. 2 Repetition of Studies Under certain circumstances, these studies should be repeated if variations and changes are made to the product, depending on the photostability characteristics determined at the time of initial filing. 3 Scope The guideline primarily addresses the generation of photostability information for submission in Registration Applications for new molecular entities and associated drug products.

3. Light Sources Option 1 Light sources like artificial daylight fluorescent lamps, xenon, or metal halide lamps emit light similar to D65/ID65 emission standards, with D65 for outdoor daylight and ID65 for indoor indirect daylight. Filters may be fitted for radiation below 320 nm. Option 2 Option 2 involves exposing the sample to both cool white and near fluorescent lamps, with a cool white lamp producing ISO 10977 output and a near UV lamp distributing 320 to 400 nm with maximum energy emission 350 nm and 370 nm.

4. Procedure 1 Confirmatory Studies Samples should be exposed to light providing an overall illumination of not less than 1.2 million lux hours and an integrated near ultraviolet energy of not less than 200 watt hours/square meter . 2 Actinometric Procedure Samples can be tested using a validated chemical actinometric system or calibrated radiometers/lux meters. Protected samples can be used as dark controls to evaluate thermally induced change contribution to observed change. An example of an actinometric procedure is provided in the Annex to monitor exposure to a near UV fluorescent lamp.

5. Drug Substance Forced Degradation Testing Forced degradation testing studies are undertaken to evaluate the overall photosensitivity of the material for method development purposes and/or degradation pathway elucidation. Samples should be in chemically inert and transparent containers. Exposure conditions may vary depending on the drug substance's photosensitivity and light source intensity.
Decomposition products may be observed under forcing conditions, useful for developing analytical methods. Confirmatory Testing Confirmatory studies provide information for handling, packaging, and labeling. Typically, one batch of drug substance is tested during the development phase, followed by photostability characteristics confirmation on a single batch if the drug is photostable or photolabile. If the results of the confirmatory study are equivocal, testing of up to two additional batches should be conducted.

6. Presentation of Samples Transparent Containers Samples should be in chemically inert and transparent containers to minimize the effects of changes in physical states. For solid drug substances, place them in a glass or plastic dish and cover with a transparent cover. For liquid drugs, expose them in chemically inert and transparent containers. Sealed Containers Efforts should be made to ensure that the effects of changes in physical states are minimized, such as sublimation, evaporation, or melting. Possible interactions between the samples and any material used for containers or for general protection of the sample, should also be considered and eliminated wherever not relevant to the test being carried out.

7. Analysis of Samples 1 Physical Properties Examine the samples for any changes in physical properties, such as appearance, clarity, or color of solution. 2 Assay and Degradants Assay and degradants should be analyzed by a method suitably validated for products likely to arise from photochemical degradation processes. Sample consideration Solid drug substance samples should be representative in individual tests, and homogenization of the entire sample is necessary. Analysis should be performed alongside protected samples used as dark controls.

8. Judgement of Results Forced Degradation Studies Designed to provide suitable information to develop and validate test methods for the confirmatory studies. Identifying photolytic degradants. Confirmatory Studies Identify precautionary measures needed in manufacturing or formulation and whether light resistant packaging and/or special labeling is needed to mitigate exposure to light.

9. Drug Product Sequential Testing Testing should be carried out in a sequential manner starting with testing the fully exposed product then progressing as necessary to the product in the immediate pack and then in the marketing pack . Testing should ensure the product is adequately protected from light exposure. Batch Selection Only one batch is tested during the development phase, and photostability characteristics should be confirmed on a single batch selected as described in the Parent Guideline. If results are ambiguous, two additional batches may be conducted. Exception Testing for products impenetrable to light, like aluminium tubes or cans, should be conducted on directly exposed drug products. Infusion liquids and dermal creams may be tested for photostability, with testing based on directions for use.

10. Presentation of Samples Sealed Containers Efforts should be made to ensure that the effects of changes in physical states are minimized, such as sublimation, evaporation, or melting . Possible interactions between the samples and any material used for containers or for general protection of the sample, should also be considered and eliminated wherever not relevant to the test being carried out. Transparent Containers When testing drug product samples outside the primary pack, present them in a similar condition and position them for maximum exposure to light as drug substance. For example, tablets, capsules, etc., should be spread in a single layer . If direct exposure isn't possible (e.g., due to oxidation of a product), place them in a protective, transparent container(e.g., quartz). Immediate/marketed container Test drug product in immediate container or marketed form, placing samples horizontally or transversely for uniform exposure. Adjust conditions for large volume containers (e.g., dispensing packs).

11. Analysis of Samples 1 Physical Properties Examine the samples for any changes in physical properties, such as appearance, clarity, or color of solution, dissolution/disintegration for dosage forms such as capsules, etc. 2 Assay and Degradants Assay and degradants should be analyzed by a method suitably validated for products likely to arise from photochemical degradation processes. Sample consideration To ensure accurate testing, use a representative portion of powder samples in individual tests, and conduct testing on appropriate composites for solid oral dosage form products (for example, 20 tablets or capsules). Similar sampling considerations apply to materials like creams, ointments, and suspensions that may not be homogeneous after exposure Analyze exposed samples alongside protected samples as dark controls. .

12. Judgement of Results Depending on the extent of change special labeling or packaging may be needed to mitigate exposure to light Photostability studies should consider other stability studies to ensure product meets shelf life specifications, as per ICH Stability and Impurity Guidelines.

13. Quinine Chemical Actinometry Option 1 To analyze a solution, place 10 ml solution in a 20 ml colorless ampoule as a sample and 10 ml as a control. seal it hermetically, wrap in aluminum foil to protect completely from light, and use this as the control. Expose the samples and control to a light source for hours, then determine their absorbances at 400 nm using a 1 cm path length. Calculate the change in absorbance . Calculate the change in absorbance, ∆ A = AT - Ao . The length of exposure should be sufficient to ensure a change in absorbance of at least 0.9. Option 2 Fill a quartz cell with a sample and a control, wrap in aluminum foil to protect completely from light, and use this as the control , then expose them to light for hours. Determine absorbances at 400 nm and calculate the change in absorbance. Use alternative packaging configurations or validated chemical actinometers if needed . Calculate the change in absorbance, ∆ A = AT - Ao . The length of exposure should be sufficient to ensure a change in absorbance of at least 0.5. The actinometric procedure for monitoring UV exposure to a near UV fluorescent lamp involves preparing a 2% weight/volume aqueous solution of quinine monohydrochloride dihydrate , which should be calibrated for the light source used.

14. Glossary Immediate Pack The constituent of the packaging that is in direct contact with the drug substance or drug product, and includes any appropriate label. Marketing Pack The combination of immediate pack and other secondary packaging such as a carton.