cGMP Laboratory Services

VIMTA’s method development and validation teams have extensive experience with developing and validating analytical methods for the determination of purity or other critical attributes of materials from development to the commercial phase of drug manufacture. Our cGMP laboratories feature a broad and diverse set of instrumentation to assist you with your analytical needs while meeting critical timelines.

Drug method development and validation include chromatographic, spectroscopic, microbiology, physical characterization, “wet-chemical” and titration techniques. Methods are developed while keeping in mind customer requirements for ease of use and transfer. Validations are performed as per ICH guidelines and also for any specific regulatory requirements of your product. We offer mini validations or verifications (limited parameters such as specificity, linearity, accuracy, etc.) to support early-phase formulation and packaging development studies, in addition to full scale ICH validation (linearity, precision- repeatability and intermediate precision, accuracy, specificity, LOD, LOQ, range, robustness and stability of test solutions) for late-phase and commercial products.

High Pressure Liquid Chromatography (HPLC, UPLC & UHPLC)

• Identification and assays
• Stability indicating methods for drug substances and drug products
• UOD / Content Uniformity / Blend Uniformity
• Isocratic HPLC methods to support nonstability indicating tests (Dissolution, Content Uniformity)
• Development of rapid UPLC and UHPLC methods
• Modernization of old HPLC methods to UPLC methods
• Chiral, Gel Permeation, Reversed-phase, Normal-phase, Ion-pairing, and Ion Exchange separations
• Forced degradation studies
• Isolation and characterization of degradation impurities
• Related substance studies
• UV / VIS (including PDA), Refractive Index, Fluorescence, Evaporative Light Scattering, and Mass Spectroscopic detection

Gas Chromatography (Gc)

• Organic Volatile Impurities (OVI) and Residual Solvents methods for drug products, drug substances, and raw materials
• Assay for non-solvent volatile impurities and intermediates
• Headspace and direct injection sample introduction for packed and capillary columns
• Flame Ionization (FID), Thermal Conductivity (TCD), and Mass Spectroscopic (MS) detection

Ion Chromatography (Ic)

• Analysis of inorganic cations and anions; organic acids and bases; amino acids and proteins
• Analysis of mono, di, oligosaccharide, and polysaccharide and their derivatives

Karl Fischer Moisture Titrations

• Moisture testing of powders, capsules, tablets, suspensions, liquids, and lyophilized products
• Coulometric titration instrumentation for low-level moisture determinations
• Drying oven sample introduction and / or Ketone-specific reagents for difficult sample matrixes

Physical Size Characterization

• Polymorphic Quantification to determine impurity content by pXRD, FT-RAMAN
• Identification of Polymorphic form of drug substance in finished product by pXRD
• Determination of Cyrstallinity in drug substance and finished product by pXRD
• Identification of polymorphic form of drug substance and impurities by DSC
• Wet or Dry Dispersion by Particle Size Analyzer [D(10), D(50), D(90)]
• LOD & Carbonate Estimation of drug substance and drug product by TGA

Dissolution and Drug Release

• Discriminatory dissolution rate study
• Water soluble, sparingly water soluble molecules
• Immediate release and modified release formulations
• Single medium dissolutions, 2-stage dissolutions, 12- and 24-hour dissolutions
• Multi-media dissolution
• Intrinsic dissolution testing
• Alcohol dose dumping studies
• Comparative studies
• Apparatus 1, 2, and 6; manual or automated sampling
• UV / VIS and HPLC analysis options

Cleaning Methods

Genotoxic impurities identification and quantification

Leachables

• Analysis of leachables samples in Extractables and Leachable studies, for accurate detection and quantification of analytes
• Method development and validation by LC-MS / MS, GC-MS / MS, ICP-MS, IC, HPLC

Trace Metals (ICPMS, ICP-OES, AAS)

• Analysis of raw materials, drug substance, drug product
• Method Development, Validation and Transfer

Other Analytical Techniques

• UV / VIS, TOC, Viscometer, Polarimeter, Refractometer, Osmometer, Fluorometer, FTIR, pH, TLC, Ion-selective Electrodes, Potentiometric and Colorimetric Titrations

Microbiology

• AET & PET
• Microbial Limit Test
• Sterility Test
• Bacterial Endotoxin Test
• Antimicrobial Effectiveness Test
• Preservative Efficacy Test
• Disinfectant Efficacy Test
• Microbiological Potency Assays
• Water Systems Validations

Potential interactions between drug product and its

• container closure systems and
• manufacturing process contact material

are an important regulatory consideration for Pharmaceutical and Biopharmaceutical companies. Each drug application (human drug or biologic) filing should contain enough information to show each proposed container closure system and safe and suitable for its intended use. The type and extent of information that should be provided in an application will depend on the dosage form and the route of administration.

As per cGMP regulatory requirements (21 CFR Part 211.94 (a)), drug product containers and closures shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality or purity beyond the official or established requirements, and therefore drug product should be evaluated for any chemical contaminants or impurities that maybe generated during manufacturing or storage. This evaluation is performed by extractable and leachables studies.

Extractables are any chemical species that can be removed from a packaging component or device or manufacturing process contact material, into solvents under controlled laboratory conditions (e.g., component is cut in pieces and incubated with solvent). Leachable is an extractable that actually migrates into a drug product under storage conditions. Not all extractables are leachables and neither are all leachables correlatable to extractables.

Container Closure System refers to the sum of the packaging components that together contain and protect the dosage form. This includes both primary and secondary packaging components.

VIMTA can provide customized protocol driven extractables and leachables testing services to help you ensure that your product meets applicable regulations requirements and is safe for the patient. Our scientific team, with experience of over 200 E & L studies under its belt, is well versed with the science, regulations, guidances and standards related to E&L studies. Our data has been submitted to, and well accepted by, US and European regulatory authorities.

• USP<1663> Assessment of Extractables Associated with Pharmaceutical Packaging / Delivery Systems
• USP<1664> Assessment of Drug Product Leachables Associated with Pharmaceutical
• PQRI (March 2007) Guidelines for Reporting and Qualification Thresholds for Leachables in Parenteral and Ophthalmic Drug Products
• PQRI (Sept 2006) – Guide Safety Thresholds and Best Practices for Extractables and Leachables in Orally Inhaled and Nasal Drug Products
• USFDA Guidance for Industry (1999) on Container Closure Systems for Packaging Human Drugs and Biologics
• USFDA Guidance for Industry (2002) on Nasal Spray and Inhalation Solution, Suspension and Drug Products Points of Consideration
• USFDA – 21 CFR 600.11] – Biological products – (b) Equipment – (h) Containers & Closures
• EMA – CPMP / QWP /4359/03 – 2005 – European Medicines Agency – Guideline on plastic immediate packaging materials
• ICH Q3A/B (R2) – 2006 – Impurities in New Drug Substances/Products.

• Packaging material assessment and development of customized study protocol
• Controlled extraction utilizing PQRI protocols (with minimum 3 solvents)
• Qualitative and quantitative analysis of extractables using HPLC, LC-MS / MS, GC-MS / MS, ICP-MS, IC etc
• Identification of unknown compounds
• Method development, optimization and validation of controlled extractable study for routine control of container closure system

• Method development and validation for quantification of specific leachables in the drug product
• Identification & quantification of all compounds not found in control product
• Leachables monitoring in stability study samples
• If end of shelf life samples are not available, we can take up ICH stability testing to generate the leachables
• Correlation establishment of potential leachables and actual leachables
• Evaluations of results for toxicology issues - A toxicological evaluation should be made of the extractables and leachables from the container closure system. The assessment should include appropriate In Vitro and In Vivo tests. Alternatively, we can also support with applicable citations and additional safety data

• Label Migration Studies (Gum and link migration studies)
• Delamination Studies (Glass Vials, Syringes etc.)
• Packaging Safety & Toxicity Analysis (In-house GLP certified, AAALAC accredited preclinical study capabilities)
• Controlled Extraction Studies for Raw Material Control
• Stability Studies
• Genotoxic Impurity Studies
• Physical Characterization Testing

• Inhalations
• Opthalmics
• Parenterals, injectables
• Oral vaccines
• Topicals
• Dermal Pathches
• Implants
• Solid dosage forms

Effective May 1, 2016, new USP/NF requirements have been published for plastic packaging systems used for pharmaceutical products to establish the suitability of plastic packaging systems and their material of construction for therapeutic products. The new requirements affect packaging systems for pharmaceutical products that are not yet approved by the regulator for marketing. If the packaging system is currently being used with a pharmaceutical product that is on the market, it does not require testing to the new requirements. However in case of modifications, to the plastic packaging system or its material of construction, the packaging system must be re-tested as per USP 661.1 and 661.2. If the packaging system is changed in a way that does not alter its materials, then it does not need testing.

VIMTA provides testing of packaging material as per USP 661.1 and USP 661.2 Tests offered include:

VIMTA tests drug raw materials and excipients routinely as per latest pharmacopoeial requirements ( USP, BP, EP, IP, JP), including the following tests:

• Identification Tests
• Trace metal analysis by using AAS and ICP-MS techniques
• Organic Volatile Impurities and Residual Solvents as per USP
• Heavy metals

VIMTA is one of India’s largest providers of stability testing and storage services. Multinational corporations in OTC, Rx, and Animal Health around the world trust VIMTA’s services. More than 80% of our capacities are utilized by companies located in Americas and Europe. We offer substantial cost-savings compared to investing in your own storage chambers, related space, manpower and testing equipment thereby freeing up your resources for your core activities.

We conduct stability studies as per ICH guidelines and also offer customized stability programs. Our facilities fulfil all criteria of international cGMP requirements. We are WHO pre-qualified and have been successfully audited by USFDA. Thorough risk assessment has been performed while setting up the stability storage and testing infrastructure and robust systems are installed to control and manage the risks.

Our state-of-the-art stability chambers, with close to ~4,50,000 Liters capacity, are equipped with advanced chiller based technologies, backup systems, redundant power backup, alarms system, and automated temp / RH excursion mobile phone notifications. All stability chambers are monitored 24 x 7 x 365 by a facility administration team through a building management system that records temperature and humidity every fifteen minutes and raises alerts as per pre-set criteria. Chambers are managed through a robust preventive maintenance program with support of in-house engineering team as well as vendor Annual Maintenance Contracts.

• Clinical stability
• Developmental stability
• Follow-up stability studies
• Registration stability studies
• Transport stability studies
• Freeze thaw cycling stability studies
• Photostability studies
• Extractables and Leachables

• 25°C / 60 % RH
• 30°C / 65 % RH
• 40°C / 75 % RH
• 25°C / 40 % RH
• 30°C / 75 % RH
• 50°C
• ≤ - 70°C
• - 20°C
• 5°C
• 15°C
• Photostability

In addition to the above conditions, we can set up stability chambers for other temperature and humidity conditions.

Our Stability Testing laboratory is supported by Wide Range of Instrumentation, including manual / semi-automated / automated dissolution apparatus such as CALIPER Multi Dose G3, Tablet Processing Work station (TPW) for uniformity testing.

Comprehensive testing capabilities include assay, dissolution, Karl Fischer, hardness, disintegration, friability and characterization of impurities and degradants.

We offer customer specific contract labs in FTE model or fee for service model for both large scale and small scale stability testing requirements.

Features of our Customer Specific Contract Labs Includes:

• Customized lab setup with equipment make and models as per customer product portfolio requirements
• Dedicated manpower, project management executive and QA personnel
• Laboratory tuned to 24/7 operations, if required
• Securely connectable to customer LIMS for concurrent data access
• Implementation of customer quality management systems for stability management, OOS management etc
• KPI driven process to monitor for in-time services. We have 10 years track record in delivering KPIs between 98% to 100%
• Co-management of the lab with on-site customer representative, if desired

VIMTA offers analytical support to evaluate new products in development with marketed products of the same class. Services include:

• Assay
• Dissolution
• Impurity profiling
• Stability studies
 

Routine, non-routine and everything in between. Our veteran trace metals group delivers true cGMP results with the following services:

• Elemental analysis of raw material, drug substances and drug products
• Complete program for USA 232 and USP 233 Elemental Impurities
• Determination of metal counter ions for drug substance salts
• Method development, validation and transfer
• Conventional and microwave digestion sample preparation
• ICP-MS, ICP-OES, GFAAS, FAAS, and Cold Vapor Mercury instrumentation

Under the class of In Vitro studies, we offer the following services:

In vitro dissolution testing may be a useful tool to forecast the In Vivo performance of drug products and potentially reduce the number of bioavailability / bioequivalence (BA/BE) studies required. For drug products that have low systemic absorption, In Vitro binding studies are considered as an acceptable alternative to BA/BE studies by regulators including USFDA.

To support your R&D and regulatory filings, VIMTA offers fast turnaround physical characterization services including polymorph characterization, thermal analysis, spectroscopic analysis and particle size determination.

• Screening
• Identification (Qualitative)
• Estimations (Quantitative)
• Melting Point/Range for Drug Substances
• Exotherm and Endotherm Determinations
• Decomposition temperature
• Glass Transition
• Thermal Analysis as per USP for Plastics i.e. Polymers (HDPE, LDPE, Homopolymer Polypropylene and Co-Polymer Polypropylene)
• Loss on Drying in DS & DP
• Residue on Ignition (NCEs)
• Hydrate Confirmation in DS
• Carbonate Content Estimation in DS
• Bound Moisture Estimation

• Monitoring the stability of polymorph


• Method development, validation, method verification for polymorph identification and quantification


• Particle size distribution (morphology) through wet and dry methods

Powder X-Ray diffractometer (pXRD) : Bruker D8 Advance Integrated Reflection, Transmission & Capillary mode Ability to Handle

• Small Sample Quantities (-10 mg)
• Solids, Ointments, Gels, Suspensions, Emulsions
• Direct Tablet Analysis Without Grinding
• Hygroscopic Materials

• Aeros (Dry dispersion)
• Hydero MV (Wet Sample Dispersion)

VIMTA offers a full gamut of microbiological testing, be it batch release testing or sterility, antimicrobial efficacy or microbial contamination, endotoxin analysis, microbial identification, or method development and validation. Our purpose built cGMP compliant microbiology laboratory is fully equipped for testing of raw materials, medical devices and finished products. We have over 25 years of experience on a wide array of dosage formulations.

• Sterile Pharmaceutical Products, Injectables, Vaccines, Hospital Ware, and Surgical Items
• Two methods – Direct Inoculation, Membrane Filtration Nitrofurans

• Using Hamonized Pharmacopoeial Method or Customer Methods
• Total Yeast and Mold Count (TYMC)
• Total Aerobic Microbial Count (TAMC)

Process water / Reagent water quality as per pharmacopoeial monographs or customer specific requirements

• Microbial Limit Test
• Antimicrobial Effectiveness of Preservatives/Preservative Efficacy Test (AET / PET)
• Bacterial Endotoxin Test
• Sterility Test
• Disinfectant Efficacy Test

• Conventional: Microscopic, biochemical and serological
• Genetic analysis through microseq®:

We are recognized industry-wide as the "gold standard" in culture identification. Gene sequencing is based on the phylogenetic analysis on rDNA sequences. Gene sequencing offers a number of distinct advantages over older identification methods, including:

• Shorter turnaround time for yeast and mold identification compared to traditional ID methods
• Increased accuracy and reproducibility over traditional phenotypic identification methods
• Higher specificity than traditional phenotypic ID methods
• Identification of organisms by genus and species

Media growth promotion (media fertility) testing

• Test performed as per USP 61 and ISO / TS 11133-1 & ISO/TS 11133-2
• Growth promotion test- Qualitative
• Growth promotion test- Quantitative, % recovery

Work Place Monitoring

• Testing performed for Air / Clean rooms / Manufacturing facility / Equipment/ Personnel
• Bioburden / Viable count: Settle plate method (4 hrs exposure)
• (i)Aerobic microbial count & (ii) Combined yeasts & molds by Fallout or Swab testing (in buffer solution.): AMC, Y & M, Coliforms
• Swab testing (in buffer solution.): AMC, Yeasts & Molds, Coliforms, E.coli Salmonella and Enterobacteriacaes
• Enumeration of Lactobacillus acidophilus in dairy and pharma products
• Detection of contamination of Bacillus subtilis & Bacillus cereus in pharma products
• Air sampling (By air sampler)
• Media plates / swabs for sampling
• Other parameters on request

Healthcare products & Disinfectants

• Evaluation of antimicrobial properties of different healthcare products as per customer supplied protocols / ASTM methods (ASTM 1115 & ASTM E 1174). Studies include MIC testing, Neutralization testing as per ASTM 1054-02, antimicrobial effectiveness testing of personnel hand washes
• Germicidal value
• Phenolic disinfectants-IS 1061
• Rideal walker coefficient (RWC)
• Staphylococcus aureus coefficient (SAC)

VIMTA offers ELISA assay services for the following

Drug products and drug substances are analysed routinely at VIMTA as per the latest pharmacopeia (USP, BP, EP, IP, JP) or customer specified procedures and specifications. All methods are used only after due verifications or validations. Our pharmaceutical testing laboratories are equipped with a full array of analytical instrumentation to perform the following tests.

NBCDs or Non-Biological Complex Drugs are neither biologics nor small molecules, they are a mixture of the two. They have higher molecular weight, and are synthetic compounds that are complex in structure and can form branched structures such as polypeptides, swelling polymers, liposomes and colloidal iron carbohydrates. Some examples include Iron Sucrose, low molecular weight heparin (LMWH), Glatiramer Acetate (GA) etc. Due to their complexity and specific composition mix, these compounds cannot be fully identified, characterized, quantitated and / or described by physiochemical means to define their pharmaceutical properties.

VIMTA offers US-FDA and EMEA guidance based analytical characterization as well as potency estimation (Lot Release Assay) services.

• Identity using RP-HPLC, SAX-HPLC, CE
• Assay
• In Vitro activity
• Impurity characterization using Octet K2, HPLC or LCMS, RT-PCR, Bioplex 200
• In Vivo Immunogenicity using ELISA
• Equivalence in the fragment map

GLP compliant full range of analytical support services are provided by VIMTA to assist in preclinical studies. We have extensive analytical and bioanalytical infrastructure capable of supporting your requirements for scientifically sound, reliable, compliant and fast turnaround time data. We offer:

It is of critical importance for pharmaceutical manufacturers to put into market compliant products. Any product defects would create losses for the manufacturer due to recalls and legal litigations, not to mention the adverse impact on the brand value. At VIMTA we help you investigate product defects so that effective solutions can be taken up to fix the root cause of the failures and prevent recurrences.

Our diverse analytical knowledge and instrumentation capabilities help to investigate product defects caused by manufacturing processes. We deploy varied technologies such as SEM, FT-IR, GC / MS, LC / MS, DSC, TGA, etc., to identify the contaminants or cause of product defects. We are sensitive to your tight timeline needs and can provide express services.

VIMTA is the first WHO prequalified Quality Control Laboratory in Asia for Medicines Program Inspection. VIMTA offers global procurement agencies and manufacturers, pre-shipment inspection services for quality and quantity certification. Services include:

• Supervision of loading and dispatch operation
• Container stuffing and sampling supervision
• Quality testing and analyses of product as per importing country’s specific standards / international standards /contractual specifications
• Consignment Certification as per importing country's specific standards/contractual specifications

VIMTA offers comprehensive Pharmaceutical Grade Water testing as per USP, BP, WHO Guidelines, EU Guidelines, and US-EPA Specifications. We serve more than 90% of the USFDA and WHO approved pharmaceutical manufacturing plants located in India, to test their water for pharmaceutical manufacturing processes.

VIMTA, the pioneer in India for pesticide residue testing analysis, uses state of the art instrumentation and has extensive capabilities in pesticide residues and disinfectant residues.

• IS 10500, 2012 Amendment 1, 2 & 3 (Drinking Water)
• US EPA guidelines
• USP <1231> Water for Pharmaceutical Purposes

• Water Testing as per US EPA and IS 10500 standards
• Inlet & Outlet Water Analysis

• Soil and Environmental Analysis for Pharmaceutical Contamination
• Environmental Microbiology & Consultancy Testing

VIMTA offers testing of contraceptives such as condoms, copper-T and pills.

Male contraceptive performance testing is required in many markets and by the WHO. Applicable Standards include ISO 4074: 2015 (Natural Latex Rubber Condoms), WHO’s Specification, Prequalification and Guidelines for Procurement: 2010, Schedule 'R' of Drugs & Cosmetics, and ASTM D3492 (Rubber Contraceptives). The quality tests include:

• Description and identity mark
• Visible defects
• Length, width, thickness
• Color fastness
• Quantity of lubricant
• Burst volume and pressure (before and after aging)
• Water leakage test (freedom from holes)
• Force and elongation at break
• Shelf life and stability
• Package integrity
• Packaging and labeling
• Copper-T testing is as per ISO 7439 / NDA 18-680. Tests include:
• Pouch integrity
• Pouch contents
• Length of tie
• Position of copper collar
• Weight of wire
• Outer diameter
• Pull force
• Pouch burst strength

Along with the above tests, VIMTA also offers biocompatibility testing as per ISO 10993.

Contraceptive Pills are tested as per IP 2014, and can also be tested for any other specific Standards.