Pharmaceutical Regulatory Affairs: Open Access

In the new Risk-Based (RB) environment of clinical trials, policy to prevent and address misconduct and fraud by Clinical Research Associates (CRA) is virtually nonexistent. To date, misconduct of CRAs and its potential cost to patients and sponsors has not been studied, and thus, has not been addressed. Through strong policy change, it is time for regulators to voice a firm stance that misconduct and fraud will not be tolerated by any member of the scientific community.

Traditionally, onsite monitoring has been the standard for quality control with its emphasis placed on Clinical Research Site (CRS) conduct. Quality Assurance (QA) audits retrospectively sample CRS work-product for any possible mistakes or misconduct missed during the monitoring process. There are no regulated standards for how onsite monitoring visits are conducted, during which there is very little oversight of CRAs. Misconduct and fraud by CRAs is not well documented in the literature or in FDA guidance, and with the adoption of Risk-Based Monitoring (RBM) methods, there will be far less oversight of CRAs creating room for their potential misconduct and fraud. The resulting financial cost to sponsors, and risk to patient safety and rights, cannot yet be estimated. Regulators must make confronting CRA misconduct a priority.

In order to market any medical device, marketing authorization from Regulatory authority is required. The process of gaining authorization is complex, multistep and requires review of information by competent authorities. Upon scrutinizing the information furnished by Manufacturer, marketing authorization is granted by the concerned Regulatory authority. In the USA, manufacturers are required to apply to United States Food and Drugs Application (USFDA) for Marketing Authorization. There are two types of applications in USA; 510 (k) and Pre-Market Application (PMA). In EU, National Authorities give approval for marketing medical devices. A system of third party compliance is followed, where Notified Bodies (Third Party) ensure Quality Assurance, pre and post approval. In India, Central Drugs Standard Control Organization (CDSCO) approves devices for sale and import. Medical Devices are regulated under CLAA scheme. The Drug Controller General of India (DCGI) is the central licensing authority for medical devices. This paper attempts to capture information on regulations of Medical Device in three regions namely; USA, EU and India and compare provisions of Market authorization in the respective regions, and further, for the readers, make this complex subject easier to grasp.

The Animal Welfare Act (AWA; 1990) requires the reduction in use of purpose bred animal subjects in bona fide research conducted in drug development. The National Institutes of Health (NIH) Revitalization Act of 1993 also requires its Director to reduce the number of animals used in government funded research as well as promoting those specific study protocols that provide valid and reliable data using only one gender. The consensus between the pharmaceutical industry and FDA was that a valid and reliable set of abuse liability studies did NOT require the inclusion of both male and female subjects. In recent pre-study protocol reviews, FDA has required the inclusion of both males and female animals in all three core abuse liability assays, basically doubling the total number of animals used on a single study design. NIH/FDA policy does allow for exceptions to the new rule. We provide evidence to establish a defence of a more balanced approach to these study designs that complies with the AWA and the NIH Revitalization Act by reducing the use of laboratory animals in preclinical research and to align the study designs with current goals of the International Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC).

To study the product life cycle management in the regulated market of Europe Under this title the scope of work is defined as: To study the practical aspects of different phases of life cycle of generic sterilized injectable product in regulated market of Europe, to study the European standards and requirements for registration of injectable drugs, to study the lifecycle start from the product identification by market surveying and till its withdrawal or renewal in the Europe market, the data may contain official information to be taken from the EMEA guidelines, live case studies and live operational projects at International Regulatory affairs department at Claris life sciences Ltd to study, prepare, compile and submit the data according to the CTD format in the regulatory agencies of Europe as critical phase of life cycle. The pharmaceutical industry is now perhaps the most highly regulated of all industries demanding a high level of information to be submitted to governments before a pharmaceutical product is brought to the market place. Each country holds different regulatory department. In this scenario, the product life cycle management in regulated market of Europe upholds a significant value.

Cataract is the ocular disease that lessens the vision by making the lens opaque. It is a dysfunction of the lens resulting from opacification, which impedes the transmission of light. Oxidative stress is the main culprit of this disease which leads to clouding of the human lens. The prevention of the oxidative stress and other factors that worsen this disease can be minimizing by the intake of vitamin c and its anti-oxidative activity is helpful in reducing its outbreak in future. Whereas increase intake of vitamin C in the diet may have increases the availability in the fluid around the lens, providing extra protection.

Purpose: The Institute for Safe Medication Practices has published numerous safety alerts in regards to institutional insulin pen use focused on the misuse of insulin pens and subsequent transmission of infections. Other institutions may use floor-stock insulin; however, The Joint Commission has provided recent guidance against using multiuse vials on multiple patients. The purpose of this study is to evaluate Bronson Healthcare Group’s different methods of insulin administration to determine a cost-effective strategy while meeting regulatory requirements. Secondary endpoints will evaluate safety and nursing preference of different types of insulin delivery.

Methods: Retrospective data was collected in the form of medication safety event forms, insulin purchasing records, hospital-wide insulin usage reports, number of patient-days reports, and a nursing survey. Insulin use, purchasing data, and safety event reports were collected from August 2013 to August 2014 from Bronson Methodist Hospital and Bronson Battle Creek Hospital. The nursing survey was distributed to inpatient Bronson facilities from January 22 to February 5, 2015. Aggregate data was collected and analyzed via Microsoft Excel. Descriptive statistics were used to evaluate the primary outcome. Chi squared and t-tests were used for secondary outcomes as appropriate.

Results: By switching to short-acting insulin administered from 3 mL single-patient insulin lispro vials and pharmacy-drawn long-acting insulin detemir the hospital system could potentially save approximately $22,000 a year. Data did not support there being a safer method of insulin delivery. Nursing preference data indicated that nurses prefer delivery methods with which they are more familiar.

Conclusion: In combination with recommended best safety practices as reported by multiple nationally recognized safety organizations, we can conclude that the most cost-effective methods of insulin delivery for the Bronson Health System would be pharmacy technician drawn single doses of long acting insulin detemir and single patient 3 mL vials of insulin lispro.

Effective Processes for Quality Assurance provide an understanding and importance for support in providing perspective and understanding from day to day activities and to provide effective and advocate a culture that supports commitment to customer integrity.

Pharmaceutical research and development is an expensive, time consuming and uncertain process that may take 8-10 years to complete. Patent clock starts much before a new drug is approved for marketing and significant amount of time may be lost in the review and approval process by regulatory bodies. So in order to recoup the considerable time and resources invested in the drug development and approval process the pharmaceutical companies depend on exclusivity provisions granted by the regulatory bodies. There are several official and unofficial methods to extend term of a patent beyond 20 years, Official methods include provisions by some regulatory bodies such as Data exclusivity, Orphan drug exclusivity, Paediatric exclusivity and the 180-day exclusivity (Hatch Waxman Act, U.S. Food and Drug Administration), Supplementary protection certificate (European Medical Agency), whereas unofficial methods include altering or reformulate the existing compound to obtain a new patent by utilising polymorphism, creating combinations, stereo-selective/chiral switches, conversion to NDDS, OTC switching, authorised generics, etc. This article aims at highlighting the strategies used by Pharma giants to extend the term of their patent portfolio in order to maintain their monopoly for extended periods and the regulatory provisions in different countries to check these practices.

In the present study, a rapid, an accurate and precise Ultra Performance Liquid Chromatography (UPLC) method was developed and validated for simultaneous estimation of paracetamol and caffeine in its capsule dosage form (325 mg and 30 mg) by selecting chromatographic parameters. The UPLC method was developed using 2.1 × 50 mm, reverse phase C₁₈ column (Acquity UPLC ethylene bridge hybrid (BEH) C₁₈ 1.7 μm) with mobile phases containing 0.1% w/v H₃PO₄ and 100% v/v buffer as mobile phase A and methanol: Acetonitrile (50:50) as mobile phase B and water: acetonitrile: H₃PO₄ (80:20:0.1) as diluent and the run considered as an isocratic elution. Flow rate was 0.5 ml/min with PDA detection at (λ_max) 275 nm for paracetamol and caffeine and the injection volume was set at 2 μL with run time 7 min. The method was validated by using various validation parameters like accuracy, precision, linearity and specificity. These results show the method could find practical application as a quality control tool for analysis of the drug in its capsule dosage forms in pharmaceutical industries. The developed validated method and stability testing of new dosage forms as per ICH-Q2 (R1) and ICH-Q1C guidelines applicable for the analysis of bulk drug and in its capsules dosage form.

The review outlines the current issues of Pharmacovigilance System in the Russian Federation, namely present state of regulatory aspects of PV system in Russia, regulatory requirements in Russia and in Eurasian Economic Union, review of the causes of under-reporting of ADRs. Specific focus has been made on topical issues such as a harmonization of the requirements to the Pharmacovigilance System, currently underway in Russia, the issue of Guidelines on Good Pharmacovigilance Practice (GVP) in the Eurasian Economic Union. These actions are aimed at improving and harmonizing the rules governing the main aspects of the Pharmacovigilance System in the Russian Federation. Also the review analyses one of the most important aspects in development of a new Pharmacovigilance System-the attitude towards pharmacovigilance in patients and healthcare professionals.

Classical experimental designs have been popularly employed in establishing robust analytical methods while achieving other advantages, viz., reduction in the number of experiments and hence lower reagent consumption and less laboratory work. To achieve optimum chromatographic condition, a computer-aided Box-Behnken Design (BBD) in ion-pairing stability-indicating RP-HPLC assay of quetiapinefumarate along with its stress related substances has been investigated here, proving to be an invaluable tool in ascertaining a reliable method. The study includes forced degradation of quetiapinefumarateunder acidic, alkaline, photo, oxidative and peroxide stress conditions followed by separation of degradation products. Critical factors including buffer pH, % organic phase (acetonitrile) and concentration of hexane sulphonate (ion-pairing reagent) susceptible to influence the separation (critical resolutions) and total analysis time were investigated by response surface methodology. The best optimal separation condition as obtained was observed on an enable C-18 column (250mm x 4.6mm i.d, 5μm particle size) using mobile phase composed of Phosphate buffer (pH 2.0) containing 0.002mM hexane sulphonate and acetonitrile (74.4:25.6 v/v) at a flow rate of 1.00ml/min. The eluents were observed at 220nm using a PDA detector. Further, the method was validated to ensure its reliability and other regulatory criteria are met.

There are no legal basis for the orphan medicines mentioned in Law No. 105/2014, 31.07.2014 “On drugs and pharmaceutical service”, amended. They are regulated by this low as the other medicines authorized in Albania according to the centralized procedure. This procedure is applied for the medicines authorized from EMA and FDA. The main document for this procedure is the Certificate of the Pharmaceutical Product from EMA or FDA. Specific requirements for the centralized procedure are detailed in Decision of the Council of Ministers No. 299, 08.04.2015. Actually in Albania are authorized for marketing 14 orphan medicines; they are designed for the treatment of rare diseases as mucopolysaccharidosis II and VI, Fabry disease, Cystic Fibrosis, Acromegaly Pituitary ACTH Hypersecretion, Idiopathic Pulmonary Fibrosis, Multiple myeloma etc. These medicines are authorized in Albania since 2008 until 2017 (although the lack of specified legal basis), most of them several months to 4 years from the first authorization by EMA. To qualify for orphan designation, a medicine must meet these criteria: it must be intended for the treatment, prevention or diagnosis of a disease that is life-threatening or chronically debilitating; the prevalence of the condition in the EU must not be more than 5 in 10,000; no satisfactory method of diagnosis, prevention or treatment of the condition concerned can be authorized, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition. 60% of designated orphan medicines are intended for paediatric use. Because rare diseases are a global issue, the Agencies work closely with its international partners on the designation and assessment of orphan medicines. Recommendations: Approaching the Albanian legislation with EU legislation regarding orphan medicines and creating a data base on the extension of use of Orphan medicines in Albania.

Background: Presence of substandard and falsified anti-malarial medicines is a major concern in countries with high prevalence of malaria. Systematic assessment and monitoring of anti-malarial medicines circulating on the market is critical to National Medicines Regulatory Authorities (NMRAs) in ensuring quality of these products in the fight against the burden of malaria disease.

Objectives: This survey was conducted by Tanzania Food and Drugs Authority (TFDA) with the aim of monitoring the quality of registered anti-malarial medicines circulating on the market in Tanzania Mainland.

Methodology: Purposive sampling method was used in obtaining the samples of anti-malarial medicines from 21 out of 26 regions of Tanzania Mainland between 2012 and 2015. These medicines were collected from ports of entry, domestic manufacturers, Medical Stores Department (MSD), wholesalers, hospitals, health centres, dispensaries and retail pharmacy outlets. Samples were subjected to product information review and quality screening using Global Pharma Health Fund^® (GPHF) Mini-Lab kits. Samples failing or yielding doubtful results and ten percent (10%) of passed samples were subjected to tier two confirmatory testing using full pharmacopeial monographs at TFDA-WHO prequalified quality control laboratory.

Results: A total of 1,444 samples of oral solid formulations from different types of anti-malarials were sampled. Out of these, 132 (9.1%) failed labelling product information requirements. A high percentage of samples passed identification test by TLC (97.9%) and disintegration test (99.8%). A 4.8% (7/145) failure rate was observed in confirmatory testing of which one of the failed samples namely quinine sulphate 300 mg tablets was confirmed to be falsified.

Conclusion: These results indicate the importance of post marketing surveillance as an additional measure of assuring the quality of medicines by Regulators following marketing authorization and as a way of detecting falsified medicines circulating on the market.