Key Notes on Revised Schedule M: Phytopharmaceuticals

Last Updated on January 25, 2025 by The Health Master

Phytopharmaceuticals

Key considerations for Phytopharmaceuticals for compliance under revised Schedule M are outlined below.

Continued from: Key Notes on Revised Schedule M: Radiopharmaceutical Products

Good Manufacturing Practices for Pharmaceutical Products

Revised Schedule M: Essential GMP Guidelines for Phytopharmaceuticals Manufacturers in India

Navigating the Revised Schedule M: Essential GMP Guidelines for Phytopharmaceuticals Manufacturers in India

The revised Schedule M in India outlines specific Good Manufacturing Practices (GMP) requirements for the production of Phytopharmaceuticals.

These guidelines aim to ensure the safety, quality, and efficacy of these vital Phytopharmaceuticals products.

Key requirements

• Good Manufacturing Practices (GMP) for pharmaceutical products apply to the manufacture of Phytopharmaceuticals, with additional requirements specific to their nature.
• Quality assurance requires control of starting materials, storage, processing, and use of modern analytical techniques.
• Critical equipment qualification, process validation, and change control are essential for production consistency.
• A high level of sanitation and hygiene is necessary throughout manufacturing to avoid contamination.
• Personnel involved in production and quality control must be adequately trained on the specific characteristics of Phytopharmaceuticals.
• Premises design, construction, and maintenance must consider the potential for degradation, infestation, and microbial contamination.

• Storage areas must be well-organized, clean, and labeled to prevent cross-contamination.
• Effective cleaning methods are necessary to prevent dust generation and cross-contamination during processing.
• All incoming plant materials must be quarantined and stored under appropriate conditions.
• Reference standards for phytopharmaceuticals may include botanical samples, plant preparations, or chemically defined substances.
• Specifications for starting materials, plant preparations, and finished phytopharmaceuticals should focus on ensuring safety and efficacy.
• Finished product specifications should include tests for microbiological contamination, uniformity of weight, physical appearance, and other relevant characteristics.
• The control tests and specifications should allow for the determination of the main active constituents.

Testing Requirements

Identity and Quality:

• Manufacturers must test the identity and quality of all plant materials, plant preparations (including extracts), and finished phytopharmaceutical products.

Categorization of Testing:

• Testing approaches depend on the knowledge of active constituents:

Known and Quantifiable Active Constituents:

• Test for and quantify the identified active constituents.

Known Main Component Group:

• Test for and quantify the main group of components contributing to activity (e.g., total essential oils or a representative substance like flavonoids).

Known Marker Substances:

• If active constituents aren’t identified or quantifiable, test for known marker substances.

Other (No Quantification):

• If quantification isn’t applicable or feasible, use other suitable tests, such as fingerprint chromatograms.

Identification Methods:

Use specific identification methods to differentiate the required plant material from potential substitutes or adulterants:

• Physical/Macroscopic/Microscopic Tests
• Chromatographic Procedures (TLC, HPLC, HPTLC, GLC)
• Spectrometric Techniques (UV-VIS, IR, NMR, MS)
• Chemical Reactions

Reference Samples:

• Maintain reference samples of plant materials for comparative testing (e.g., visual/microscopic examination, chromatography).

Quantitative Determination:

• Quantify known active components (for categories a and b) and marker substances (for category c).

Method Development:

• Develop and execute quality control methods in line with specification requirements, selecting tests characteristic of the analyte.

Fingerprint Chromatograms:

• For materials in category (d), use characteristic chromatograms (fingerprints) to track main constituents, acknowledging potential variations between deliveries and batches.

Stability Studies

Stability Data:

• If an expiry date is given for plant material or preparations, supporting stability data must be available. Stability data is always required for finished products.

Comprehensive Stability Assessment:

• Since the entire plant material is considered the active ingredient, simply determining the stability of known active constituents is usually insufficient.

Chromatographic Analysis:

• Use chromatography to trace changes during storage, demonstrating that the identified active ingredient (if any) and other substances remain stable and within defined limits.

Consistent Fingerprint Methods:

• Use fingerprint methods for stability studies that are as similar as possible to those used for quality control.

Established Methods:

• Use widely accepted methods for assaying identified active ingredients, constituents with known therapeutic activity, and markers.

Additional Tests:

• Emphasize other tests (moisture content, microbial contamination, dosage form control) to determine finished product shelf-life.

Preservative/Stabilizer Monitoring:

• Monitor the stability of preservatives and stabilizers. If none are used, perform alternative tests to ensure self-preservation over the product’s shelf-life.

Storage Conditions:

• Store stability study samples in the containers intended for marketing.

Batch Inclusion:

• Include the first three commercial production batches in the stability monitoring program to confirm the expiry date.
• Fewer batches may be acceptable if previous data (including pilot batches) indicates stability for at least two years.

Ongoing Stability Studies:

• Document a protocol for ongoing stability studies, typically involving one batch per year in a monitoring program.

Packaging and Labeling

Packaging Material Control:

• Store packaging materials properly and implement controls to prevent the use of incorrect labels and cartons.

Container Cleaning:

• Thoroughly clean and dry all containers and closures before packing.

Label Information:

• Provide adequate label (or package insert) information: composition, indications/actions, directions for use, cautions, adverse reactions (if any), and expiry date.

Quantitative Composition:

• Unless fully justified, state the full quantitative composition of phytopharmaceutical ingredients on the label.
• If not possible, list at least the main ingredients on the label and the full qualitative composition on the package insert.

Expression of Active Ingredients:

Express qualitative and quantitative particulars of active ingredients as follows:

Comminuted/Powdered Plant Materials:

• State the quantity of plant material or, if constituents with known therapeutic activity are unidentified, state the quantity of the preparation. Alternatively, provide a range corresponding to a defined quantity of constituents with known therapeutic activity.

Plant Preparations (Beyond Commination):

• State the nature and concentration of the solvent and the extract’s physical state.
• Also indicate the equivalent quantity or ratio of plant material to preparation (if therapeutic activity is unknown).
• If therapeutic activity is known, provide a range corresponding to a defined quantity of the constituents.

Solvent Information:

• Identify the composition of any solvent or solvent mixture used and the extract’s physical state.

Added Substances:

• If any substance is added to adjust constituent levels or for any other purpose, describe them as “other ingredients” and the genuine extract as the “active ingredient.”
• If different extract batches are used for adjustment, the final mixture is considered the genuine extract and listed as the “active ingredient.”

Please note: This information is for general guidance only and may not be exhaustive. Refer to the official regulations and any applicable guidance documents for specific requirements and interpretations.

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Compiled by:
Rakesh Dahiya, SDCO cum Licensing Authority, FDA Haryana

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Next: Key Notes on Revised Schedule M: Investigational Pharmaceutical products ….coming soon

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