Biotech

We created a biotech division in January 2012 at our Barcelona premises. This division was the result of a deal with the French biotech group IPSEN. Thanks to that agreement, we took over the necessary equipment, know-how and personnel with extensive experience developing biotechnology products.

With the development of biotechnology, how we treat diseases has undergone a major transformation both in terms of therapeutic approaches and the type of molecules involved. Latest-generation pharmaceuticals are moving from synthetic small molecules to large biomolecules. Some examples of this new generation of biopharmaceuticals include hormone peptides, recombinant proteins, monoclonal and therapeutic antibodies, antibody drug conjugates, fusion proteins, oligonucleotides, silencing RNA, recombinant vaccines, etc. Given the special properties of biopharmaceuticals, like their high molecular weight, high structural complexity and mode of action, the regulatory requirements for these molecules differ greatly from those for small molecules. In fact, a long list of tests is required to characterize the quality of a biopharmaceutical drug, which is known as the analytical fingerprint.

Plus, pharmacokinetic studies require specific bioanalytical methods like immunological or innovative mass-spectrometry methods. While metabolism plays a very limited role in the biotransformation of these molecules, immunogenicity has become a major safety issue. Therefore, both the FDA and EMA have published several guidelines establishing how to detect and study the spontaneous development of antibodies to the biopharmaceutical drug (ADA).

CMC

Chemistry, manufacturing and control analytical services are conducted under GMP compliance. During development, some phases may be executed according to GLP at the Client's request.

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Releasing a biosimilar product to market is extremely challenging. On the one hand, only a very well-equipped laboratory has the cappabilities to conduct this activity, ensuring purity, identity, and potency. On the other hand, the testing site should be GMP certified and have manufacturing authorization, subject to periodic inspections by regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

Working with biologic drugs involves a huge analytical effort to understand the characteristics of the whole molecule in depth. Various methods and technologies are requires to get the analytical fingerprint of the molecule. An extensive analytical characterization based on an orthogonal approach is a key element for the project's success. We offer complex characterization projects for innovative biologics and comparison of biosimilars.

Devices used for inhaled and nasal drug delivery are collectively referred to as Orally Inhaled and Nasal Drug Products (OINDPs). The range of products available is broad, encompassing inhalers (metered dose, dry powder and aqueous droplet), nebulizers (jet, ultrasonic and vibrating mesh) and nasal (aqueous based, dry powder and propellant based). Two of the main factors largely recognized as Critical Quality Attributes in the testing of OINDPs are the delivered dose and particle size distribution.

In recent years, the pharmaceutical industry has developed a better understanding of the impact of extractables and leachables on patient safety and drug product interaction, leading to increased scrutiny from regulators. A study should be conducted to determine the profile of extractables in the container closure components that are in contact with the formulation during storage and/or use.

We have extensive experience performing analytical tests for APIsexcipientsintermediate productsfinished productspackaging materials and process environment samples. The most suitable method is used, according to customer specifications or the relevant Pharmacopoeias description (EP, USP, BP, JP). If non-compendial methods need to be used, we develop and validate the method from scratch or transfer the method from the manufacturer.

We have a comprehensive knowledge in the development and validation of analytical proprietary and non-proprietary methods for excipients, APIs, intermediate products and finished products, according to the ICH Q2 (R1) in line with Q6A and Q6B. Our methods are ready for transfer to contract-giver, in compliance with EU-GMP chapter 6, performing a comparative test, a co-validation in two sites or a revalidation.

We provide full CH studies and on-going stability programmes for third parties. These services, at the client's request, can include: method transfer, method improvement, analytical standards management, storage at different conditions, scheduling of analytical timepoints, full analysis and out-of-trend (OOT) and out-of-specification (OOS) management. These tasks are always conducted according to procedures agreed upon with the client.

We provide microbiological testing for sterile and non-sterile APIs and drug products. Our fully-equipped laboratory includes a cleanroom with airlock technology and HEPA filters for the most sensitive operations. Our 4-glove isolator ISOFLEX-S is equipped with a Steritest pump and an H2O2 generator. The main advantage of using isolation technology for sterility testing is to ensure that no fals- positive results are obtained.

Both laboratories, KYMOS and PHARMAPROGRESS are GMP certified and we have a partial manufacturer authorization for Quality Control purposes. We offer the following services:

  • APIs Certificate of Analysis according to the relevant Pharmacopoeias
  • Individual parameter determination to be included in your batch Certificate of Analysis
  • Full analysis of all parameters to issue a stand alone batch Certificate of Analysis
  • Batch Testing and Batch Release of clinical batches
  • Batch Testing and Batch Release of marketing batches
  • Importation into the EU of medicinal drug products (human, veterinary or investigational)

We provide Elemental Impurities testing using ICP-MS according to ICH Q3D and European Pharmacopoeia and USP General Chapters <232>, <233> and <2232> for drug substances, excipients and drug products, including the 24 elements listed in the ICH Q3D guideline and/or others.

We can support you in conducting potency assays of vaccines for quality control in order to substitute "in vivo" testing. We can develop and validate a new method from scratch or improve on pre-existing methods or commercial kits. We can transfer these methods to your lab or keep it in house to provide you routine quality control of batches under GMP.

Revised monographs in the European Pharmacopoeia on heparin sodium (0333) and heparin calcium (0332) are in force from January 1st, 2015. These monographs include chromogenic anti-factor IIa and anti-factor Xa assays. The USP monograph for heparin sodium had been updated previously.

We have implemented and validated these challenging assays according to the USP monograph and they are ready to be used for drug products and drug substances. However, personalized method adjustments are necessary on a case-by-case basis.

Cleaning validation is a significant GMP activity to prevent contamination of biopharmaceutical products by ensuring that the processing equipment is suitable for later manufacturing processes. Potential contaminants include residues of the active pharmaceutical ingredients or their related substances, and residues from the products used during the cleaning process such as solvents or detergents. This is particularly important for highly-sensitizing compounds such as antibiotics, hormones and cytotoxics and in the case of parenteral drug products.

Bioanalysis

Chemistry, manufacturing and control analytical services are conducted under GMP compliance. During development, some phases may be executed according to GLP at the Client's request.

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In biological substances coming from preclinical and clinical studies, we have a long track record of developing and validating bioanalytical methods from scratch or working with transferred methods. Furthermore, we have a great capacity for processing samples. In order to quantify the plasma or serum levels of biologics for PK calculations, we mostly work with immunology methods such as ELISA, ECLA or RIA, but we also have experience in mass spectrometry of large molecules.

We develop new bioanalytical methods for immunogenicity studies of proteins and peptides following EMA and FDA guidelines on Immunogenicity of Therapeutic Proteins. Depending on the purpose and the stage of the research project, different studies must be conducted:

  • Determination of Binding Antibodies: screening, confirmatory and titration testing
  • Neutralizing Antibodies
  • Antibody Typology
  • Cellular Immune Response

Our expertise in cell biology enables us to implement, validate and perform cell-based assays (CBA) for several applications, including potency assays and neutralizing antibodies. We work with cells from primary cell lines, established cell lines obtained from client's cell banks and cultured at Kymos or with different kinds of cells, for example immortalized cells lines or commercial arrested cell lines.

We provide services of pharmacokinetics calculations and statistics for bioanalytical data coming from preclinical and clinical studies.

  • Non-Compartmental Analysis (NCA)
  • Compartmental modelling using built-in models or self-generated ones
  • Bioequivalence (AUC, Tmax, Cmax)

We use the Phoenix WinNonlin® software that has been properly validated according to guidelines for IT system validation.

We offer you our experience in studies on Percutaneous Absorption for topical semisolid drug products using vertical diffusion cells (or Franz cells) according to the EMA Draft Guideline on Quality and equivalence of topical products. Both In Vitro Release Test and In Vitro Permeation Test are available using the Hanson difussion Phoenix instrument.