Stability testing of active pharmaceutical ingredients is an essential procedure regularly performed to evaluate the chemical, physical and microbiological properties of products under different environmental conditions. These include temperature, humidity, light, oxygen, pH, time, and other critical factors.
Stability testing of active pharmaceutical components provides evidence on underlying therapeutic properties. These are quality, safety, efficacy, and other critical characteristics.
In the pharmaceutical industry, marketing authorization is a regulatory procedure that allows finished products to be legally marketed and distributed, which ensures that products are meeting acknowledged requirements. The process of attaining marketing authorization involves submitting detailed dossiers to the regulatory agency in charge of reviewing the quality of drugs.
Stability testing is an important procedure of the marketing authorization, which provides critical information. This comprises all information on manufacturing and inspection, and assures the drug provides specified therapeutic value.
Legislative background to consider
Stability testing of active pharmaceutical ingredients and products is to be established in accordance with the:
- WHO guidelines on stability testing of active pharmaceutical ingredients and finished pharmaceutical products, Annex 10
- ICH & FDA, Q1A (R2) Stability Testing of New Drug Substances and Products
- ICH & FDA, ICH Q3A Impurities in New Drug Substances
- ICH & FDA, ICH Q3B Impurities in New Drug Products
- ICH & FDA, ICH Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances
- ICH & FDA, ICH Q6B Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Biotechnological/Biological Products
- ICH & FDA, Q1B Photostability Testing of New Drug Substances and Products
- ICH & FDA, Q1C Stability Testing for New Dosage Forms
- ICH & FDA, Q5C Quality of Biotechnological Products
- ICH & FDA, Q1D Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products
- ICH & FDA, Q1E Evaluation of Stability Data
- FDA Guidance for Industry Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products
Stability testing must be carried out in accordance with the following restrictions:
The studies must be carried out with consideration of the registration region in the Climatic Zones I, II, III, IV.
The records must be tidily presented in an appropriate format, for example, tabular, graphical, or narrative.
When testing, it is also necessary to give enough weight to the careful analysis of the quantitative attribute that’s expected to change.
During testing, if the conducted analysis is showing batch-to-batch variability, it’s worth combining information into one overall estimate.
The documentation should include chromatographic prints.
The documentation should include test results that validate container closure system integrity to demonstrate the capability to maintain continuous sterility.
Primary data to maintain
Primary data is the essential information collected through:
- Accelerated stability testing
- Real-time stability testing
- Degradation studies
- Dissolution testing
Primary data is collected using different analytical methods — chromatography, spectroscopy, and microscopy. This data is used to establish appropriate production, clinical trials, packaging, distribution, and storage.
The data is provided by subunits with the following specialties:
- Physico-chemical lab (physical appearance, free formaldehyde, total ash, heavy metals, solubility, pH, losses during drying, residue during firing)
- Pharma-technical lab (dissolution, disintegration)
- Chromatography lab (gas, thin-layer, enantiomeric purity, residual solvents)
- Pharmacognosy lab (water soluble extractive value, essential oils, bitterness value)
- Microbiology lab (total viable aerobic count, pyrogens, sterility, antigens, potency)
- Contract lab (pesticide residues, aflatoxins, ochratoxins, elemental impurities, surface resistance)
This data might include:
- Physical and chemical properties (appearance, color, solubility, impurities)
- Degradation products to determine harmful effects
- Microbial contamination to ensure drug safety
- Environmental conditions to ensure drug stability
OCR technology to streamline stability testing
To keep stability testing regulatory compliant, pharma organizations must establish accurate record-keeping. This means, supportive documentation must be instantly accessible, unambiguous, complete, and verified.
Submitted dossiers must contain:
- Results of stress testing
- Results of photostability testing
- A selection of batches
- Accurate information on the container closure system integrity
- The justification of production, packaging, distribution, and storage
- The estimation of results
By adopting optical character recognition technology, pharma companies can automate daily record-keeping. This way, supportive documentation can be easily scanned, digitized, processed, and analyzed.
End-to-end automation might eliminate:
- Source diversity
- Unproductive, behindhand, and resource-intense information transfer
- Human error
- Complicated consolidation
OCR software is designed to eliminate traditionally manual workflows typically detaining overall productivity. By implementing computation technology, biopharmaceutical corporations can maintain obligatory records instantly accessible to stakeholders, unambiguous, complete, and consistent.
OCR systems are already being used across industries — in the healthcare segment, retail, banking, and others. Moving towards digital transformation, strategic-thinking companies significantly accelerate data gathering, digitization, processing, statistical analysis, advanced reporting, and more.
With the right tools, biopharma organizations might optimize:
- Stability coordination
- Annual stability plan monitoring
- Regular stability protocol review and approval
- New stability study initiation and creation
- Completing stability study verification and closure
- Quality analysis
- Data management
- Risk management
- Internal communication and cooperation
- Report preparation and summarization
- Control analysis
- Preparing and maintaining documentation, including protocols and reports
- Transferring data within departments
And if approached correctly, these companies might enjoy:
- Data validity and consolidation
- Record accessibility and traceability
- Thought-out resource-allocation
- Regulatory compliance
- Reduced risks
- Increased revenue
A custom management platform with integrated recognition technology might be strategically advantageous. The return of investment is expected in about 6 months, and might go beyond 1 million US Dollar in just 5 years of implementation.
A tailored management solution with complex pattern-matching algorithms provides significant business value. Thought-out workloads, employee satisfaction, insight-driven decision-making, immediate notifications, advanced analytics and reporting, as well as compliance with acknowledged regulatory standards among them.
The budget of sticking to traditionally manual routines, in particular paper-based records, is hard to measure. The resources commonly allocated to writing, transferring, processing, cutting, pasting, as well as validating (getting approval) is hard to calculate, but usually quite immense.
So, is it worth to start the transition and automate manual workflows, in particular supportive documentation? Without doubt!