Monthly Archives: March 2018

Orphan Drugs: Global Market Scenario and Regulations

Drugs and Disease

Global Market Scenario for Orphan Drugs

Orphan drugs are the drugs which are used for treatment of orphan/ rare diseases. After being neglected for a long time, the global market for orphan drugs is now witnessing a boom. The market is showing a constant growth and is expected to reach US$225 billion by 2024 due to recognition of their importance in healthcare. Other than this, the growth in orphan drugs is further attributed to recent advances in research modalities, increasing awareness and incidence of rare diseases, and improved incentives by regulatory authorities for development of orphan drugs. Favorable regulatory policies for orphan drug market in the United States have led to a fast growth of this market across the world. Pharmaceutical companies such as Actelion Pharmaceuticals Ltd., AbbVie, Inc., Alexion, Inc., Bayer AG and, AstraZeneca Plc are the key players in the orphan drug market.

Evolution of Orphan Drug Market Over the Years

As already mentioned, favorable regulations for the orphan drugs plays an important role in their increasing development and market growth. This is evident from the increasing numbers of orphan drugs in market from just 38 orphan drugs in 1983 to over 500 orphan drugs hitherto. Furthermore, over 230 orphan drugs had been approved by FDA in past decade and numbers are still increasing.

Development of Regulations and Guidelines for Orphan Drugs

Growth in orphan drug development led to emergence of US Orphan Drug Act 1983. With its’ successful outcomes, the act was then adopted by other nations in different customized forms. Below is the summary of the current regulations and guidelines for orphan drugs in different countries:

United States Orphan Drug Act

The act came into existence in 1983 and underwent further amendments in 1984, 1985, 1988, 1990 and, 1992. This act prioritized the treatment of rare diseases by facilitating research and development in field with provision of large amount of incentives for the same. Further, the act reduced the cost of developing new orphan drugs by wavering the fees at different stages of drug development such as new drug application fee, annual establishment and product fees after drug approval. Moreover, the act has a provision of tax credits on clinical research for orphan drugs along with the rights of exclusive marketing of product by pharmaceutical company for 7 years of development.

Japanese Orphan Drug Regulation

This act was formulated in 1993. As per these guidelines any drug would be categorized as orphan drug if it fulfills below mentioned criteria:

  • The disease targeted by orphan drug should be either incurable without any existing treatment or else the efficacy and safety profile of the new drug should surpass the ones already existing in market.
  • The prevalence of the rare condition must be less than 50,000; or the incidence must be 4/10,000 individuals.

The evaluation of new orphan drugs as per guidelines is done on priority basis resulting in fast track approvals and marketing authorizations. Further, pharmaceutical company would get added on incentives due to extended validity period of about 10 years. Moreover, reimbursement of 50% of drug development cost and waivers of taxes up to 6% on research and development of orphan drugs as per guidelines further ads onto the profits generation by pharmaceutical companies.

European Orphan Drug Act

This act came into existence in 1999. As per European Union (EU), the companies sponsoring orphan drug can participate in consultations and provide scientific advice related to development of orphan drugs. The fee for protocol assistance and follow-up is completely reduced by the act. Further the act waivered off all the fees for pre-authorization inspections. Moreover, there is provision for 50% reduction in fees on new marketing approval applications by large sized enterprises. The act also eliminated complete charges for not only marketing authorization, but post-approval charges are also wavered during the first year. However, this is applicable only to small and medium companies. Further profits to pharmaceutical companies can come from the provision of 10 years of exclusive marketing as per the act.

Turacoz Healthcare Solutions take an initiative to draw attention of healthcare providers and pharmaceutical companies towards the changing trend in global market scenario for orphan drugs. Further, this blog provides updated information about rules and regulations related to these drugs different countries. Turacoz provides high quality end to end scientific/medical writing support to the industry and academia. We expertise in several clinical trial related documents like Investigator Brochures (IBs), Protocols, Clinical Study Reports (CSRs), Clinical Evaluation Report (CER) and Common Technical Documents (CTDs) Prescribing Information (PI).

Medical Devices in Healthcare: Their Classification System and The Marketing Approval Process

Medical Devices

Introduction

Medical device is an essential part of healthcare system. It is utilised for diagnosis, prevention and treatment of the disease as well as for patient care. It covers a broad range of products, starting from simple bandage to drug delivery pumps. Over the past two decades, the demand of safe and effective medical devices has increased tremendously. This has been achieved by constantly updating and improving the regulatory framework and implementing them in the process. Moreover, the regulatory authorities across the world are working towards smoothening of the process of registration of the medical devices.

Medical devices have different classification systems and marketing approval processes for different regions. The classification systems and marketing approval processes for United States of America (USA), Europe (EU) and Canada have been discussed below.

United States of America

The medical devices, in USA, are regulated by US Food and Drug Administration (USFDA), while the law, 21 CFR (code of federal regulation), describes the regulations of medical devices. FDA’s Centre for Devices and Radiological Health (CDRH) regularly monitors trends that point towards future product development and is responsible for pre- and post-market supervision of devices in US.

Classification of medical devices

US classifies medical devices into three categories:

  1. Class I General Controls
  • With Exemptions
  • Without Exemptions
  1. Class II General Controls and Special Controls
  • With Exemptions
  • Without Exemptions
  1. Class III General Controls and Premarket Approval

The USFDA has established classifications for approximately 1,700 different generic types of devices and grouped them into 16 medical specialties referred to as panels. A panel is assigned to determine the class of medical device and decides for the exception applicable to the device.

Marketing Approval Process

Firstly, the medical devices are classified according to the FDA searching database meeting the requirements of Quality system regulation (QSR) for which Quality management system (QMS) is implemented according to the 21 CFR part 820. Clinical trial data are submitted for some of the devices of class II and all the devices of class III followed by submission of Investigational Device Exemption (IDE) report followed by submission of 510(K) premarket notification or premarket approval application. Some premarket submissions such as PMA (Premarket Approval), De Novo (Evaluation of Automatic Class III Designation) and HDE (Humanitarian Device Exemption) are also required for submission, if applicable. Most of the devices under class II are required to submit 510(K) clearance form whereas, the devices under class III are required to submit PMA approval letter issued by FDA. Once all the clearance is submitted, FDA quality system inspects the manufacturing facilities for its compliance with QSRs. After that, the medical device listing and registration of competent company is done by using FURLS system on the FDA website in accordance with 21 CFR Part 807. The steps for issuing market approval for medical devices in the US are depicted in Figure 1.

 

Figure 1: Steps for medical devices market approval in the US

 

Europe

There is no single body in EU, as in India and USA, to regulate medical devices. However, a decentralized procedure of marketing authorization is followed in EU for regulating medical devices. A third party, i.e. notified bodies, is responsible for issuing Quality Assurance certificates as well as for assuring post-approval compliance to QMS.

European commission has established three directives which are regulated by Medical Devices Directives (MDD) and are allocated to regulate the safety and marketing of medical devices. The three directives are:

  • Medical Device Directive (MDD 93/42/EEC)
  • Active Implantable Medical Device Directive (AIMDD 90/42/EE)
  • In Vitro Diagnostic Medical Device Directive (IVDMDD 98/79/EC)

Classification of medical devices

Europe follows a risk-based classification system which are broadly classified into 3 classes:

  • Class I – Low risk
  • Class IIa – Medium risk
  • Class IIb – Medium/high risk
  • Class III -High risk

Marketing Approval process

The market approval of medical devices in Europe is very different from the regulations in US. First the EU derivative which applies to the medical devices is identified followed by the determination of the class of the medical device according to the Annex IX. For class II and III QMS is implemented for the device in accordance with Annex II or V of the MDD. An authorized representative of Europe is then appointed who can take care of all the regulatory issues. A notified body audits QMS and all the technical documents after which the device registration is done followed by the registration of the competent authority with EU member state. Declaration of Conformity is then prepared which ensures the compliance of medical device with applicable Directive. Finally CE mark certificate for the device is affixed and placed it in market. Additionally, a Conformité Européene or European Conformity (CE) mark certificate is required to commercialize medical devices. The steps required for market approval of medical device in Europe are shown in Figure 2:

 

Figure 2: Steps for medical devices market approval in Europe

 

Canada

The medical devices in Canada are regulated by Health Canada. Therapeutic Product Division (TPD) of health Canada classifies medical devices on the basis of Risk-Based Classification System (RBCS). Health Canada follows a four-class scheme to classify medical devices according to the risk to the human body. Among the four classes, medical devices that possess lowest risk on human body fall under class I while the medical devices with high risk fall under class IV.

Marketing approval in Canada

For issuing market approval of medical device in Canada, first the class of the medical device is determined i.e. from class I to IV in accordance with schedule 1, part 1 of the Canadian Medical Devices Regulations (CMDR) SOR/98-282 as published by Health Canada. Except for class 1 medical devices, implement an ISO 13485:2003 QMS for all the devices followed by audit. Health Canada generally issues two types of licences for market approval of medical devices. These are the Health Canada Medical Device Establishment License (MDEL) and the Health Canada Medical Device License (MDL). MDEL is required for the devices that come under class I while the devices of class II and IV needs to have MDL for the device. Health Canada then reviews Canadian MDL application and Premarket Review Document.The approved application and certificates are posted on the official website of Health Canada and then the device is marketed. The steps for market approval of a medical device in Canada are shown in Figure 3:

 

Figure 3: Steps for medical devices market approval in Canada

 

Turacoz Healthcare Solution (THS) always aims to keep professionals updated about rules and regulations of drugs and devices of different countries. Turacoz is dedicated in providing scientific/medical writing support to the industry and academia. With expertise in several clinical trial related documents like Investigator Brochures (IBs), Protocols, Clinical Study Reports (CSRs), Clinical Evaluation Report (CER) and Common Technical Documents (CTDs) Prescribing Information (PI), we aim to deliver the best quality and guideline compliant documents to the pharma and different sectors of healthcare industry.

Regulations of Drug Approval in United States, European Union and Canada

Medical Devices,

Introduction

Drug regulations can be defined as the overall control of drug by following rules and regulations which are enforced by the government to protect the health and well-being of humans. They are crucial for ensuring high quality of the drug by confirming its efficacy, safety and quality. Every country has its own regulatory authorities such as the United States Food and Drug Administration (US-FDA for US), the European Medicines Agency (EMA for Europe) and Therapeutic Products Directorate (TPD for Canada which frame the regulatory requirements for development, approval, manufacturing and marketing of the drugs.

Regulations for Drug Approval in United States

USA is the main regulatory agency in the world and hence, it has the strictest standards for approving a new drug in US market. The regulator y authority of US, i.e., USFDA, is responsible for the safety regulation of the food and drug products in US. The drug approval process in US includes filing of Investigational New Drug (IND) application followed by New Drug Application (NDA).

Investigational New Drug Application

Once the drug is found to be safe, as per the reports of the preclinical trails, IND application (IND) is filed to the FDA to start the clinical trials or Phase I trial. The sponsor appointed by the firm or institution is responsible for submitting the IND application to the FDA for which a pre-IND meeting with FDA may be arranged in order to discuss the intended protocol for conducting the trial. The sponsor also provides information related to the chemistry, manufacturing details and quality control of the investigational drug.

New Drug Application (NDA)

After completion of all the clinical trials (i.e. Phase I, II and III trials), if the studies confirm the safety and effectiveness of the investigational drug, the manufacturer can file a New Drug Application (NDA) to the FDA for manufacturing and selling the drug in the US market.

Regulations for Drug Approval in Europe

The regulatory authority of the Europe, i.e., EMA, is responsible for the safety of the public in Europe. Prior to approval for marketing in EU, the applicant has to follow two regulatory steps mentioned below:

  • Clinical trial application
  • Marketing authorization application (MAA)

Clinical Trial Application

In Europe, the drug can be approved by four types of procedures depending upon the drug class and preference of the manufacturer. The four procedures are presented in Figure 1

Figure 1: Drug approval procedures followed in Europe

Marketing Authorization Application

The MAA is an application which is submitted by a drug manufacturer to the EMA in order to seek permission to market a developed drug product in Europe. MAA is approved at both, the state or centralized levels while the clinical trial application is approved at the state level only.

Regulations for Drug Approval in Canada

Therapeutic Products Directorate (TPD) is Health Canada’s federal authority which regulates the drugs and medical devices in Canada for human use. The applicant must present the scientific evidence on the product’s safety, effectiveness, and quality to the directorate in order to obtain permission to sell a drug product.

The Canada’s system of regulating a drug is quite similar to US. If an applicant wants to get marketing authorization in Canada then a new drug submission (NDS) must be compiled with clinical trial information and details of production, packaging, labelling, conditions for use and side effects must be submitted to TPD. Post-submission, it undergoes administrative screening to check the completeness of the document with appropriate format followed by review and assessment of safety, efficacy and quality. The TPD then evaluates the submission and communicates the deficiencies of the NDS to the sponsor to resolve them. After all the issues have been resolved, TPD issues a notice of compliance (NOC).

Turacoz Healthcare Solutions (THS) provides end-to-end regulatory writing support for clinical trials which includes Prescribing Information (PI), Investigator Brochures (IBs), Protocols, Clinical Study Reports (CSRs), Clinical Evaluation Reposts (CERs) and Common Technical Documents (CTDs).

Employee Empowerment

HR

Over and over we keep hearing about how employees want to feel connected to their work. How much they want their contributions to matter and impact the business as a whole. Empowering the team members is a great way to discover and develop the individual strengths, and then absorb them in new roles where they can excel.

Employee empowerment allows the employees to have control over their work. It gives a degree of autonomy and responsibility for decision-making in certain organizational tasks. Also, it encourages the employee to play a more active role in their work, involves them more in their specific role and enables them to make better, bigger and independent decisions (Figure-1).

Figure 1: Employee empowerment

 

In a corporate setting, employee empowerment can emerge out as powerful drivers for better performance, profitability and productivity for organizations (Figure-2).

Figure 2: Empowerment in corporate world

Turacoz Healthcare Solutions strongly believes in and practices employee empowerment. We take pride in providing employees with the skills, tools, information, and above all, the authority and responsibility for their work.

If you are looking to work with a team where every member is encouraged to be a performer, an achiever and a leader, come join us and be the part of our team!!! Share your profile on [email protected].

 

 

 

Challenges in Rare Disease Research: The Role of Advocacy Organizations in Overcoming these Challenges

Disease and Treatment, , ,

What is a Rare Disease

Rare disease refers to a condition that affects fewer people. The World Health Organization (W.H.O) has defined a rare disease as one with frequency less than 6.5-10 per 10,000 people. Challenges in Rare Diseases Research

Unlike the common disease, research in rare diseases encounters several challenges. They are:

  1. Recruiting, engaging, and retaining patients
  2. Designing and evaluating clinical trials
  3. Lack of funding

It is important to overcome these challenges to develop treatment for rare diseases and provide the affected patients a better quality of life. A boost in the research of rare disease has occurred in last two decades, the credit for this can partly be given to the patient advocacy groups.

Patient Advocacy Groups

Patients advocacy groups (PAGs) refer to the organizations, mostly non-profit, that are often concerned with one specific group of disorders. The history of the development of PAGs for specific disease dates to mid-1930s. Initially, the PAGs role was to provide emotional and social support to the affected patients; however, later they also started initiating and conducting research. As per the estimates, there are more than 1200 patient organizations in the U.S. alone that advocate patients with one or more rare diseases.

PAGs help patients with rare diseases in various ways as listed below:

  • They help patients seeking information on therapeutic options, the latest research, or financial aid resources.
  • They encourage research on the disorder by enrolling patients in studies and being involved in the study design. They may also help to look for volunteers and control subjects, to collect data, and analyze it.
  • They are involved in developing and updating guidelines related to disorders.
  • They provide emotional support to the affected individuals by organizing social events where they can meet other individuals affected with the same disorder.
  • They are involved in initiating and conducting research for new therapies, natural history information, management and care for their disorder.
  • They are involved in creating a registry of individuals affected with a rare disorder or a biobank of specimens.

Thus, the PAGs can help overcome the above-mentioned challenges associated with rare disease research.

A single organization is usually involved in one (or may be 2 to 3) of the above activity. The table below enlists some rare disease organizations that initiated research either with staff scientists of the advocacy groups or in partnerships with scientists from academic institutions or industry (Table 1).

Table 1: Advocacy Organizations and Their Achievements

 

These PAGs are linked to one or more bigger networks. Let us discuss one such bigger network.

Rare Diseases Clinical Research Network and Patient Advocacy Groups

The Rare Diseases Clinical Research Network (RDCRN) group was formed in 2003 by the Office of Rare Diseases Research (ORDR) National Center for Advancing Translational Sciences (NCATS).in collaboration with six other Institutes and Centers (ICs). It funded 10 Rare Diseases Clinical Research Consortia (RDCRC) and a single Data Management and Coordinating Center (DMCC) for the whole Network. Following its expansion in 2014, RDCRN collaborated with ten Institutes and Centers of the National Institute of Health and include 22 consortia and one DMCC. It was announced that these consortiums will collaborate with 98 PAGs as research partners. A recent study by Merkel et al (2016) outlines the roles patients and PAGs play in the RDCRN and reports on the PAGs’ impact on the Network’s success. The activities of PAGs are presented in Figure 1.

RDCRN: Rare Diseases Clinical Research Network; PAG: Patient advocacy group

Figure 1: Activities of patient advocacy groups

Thus, PAGs form a pillar in conducting rare disease research. They can help reach the treatment to millions of individuals with rare diseases worldwide. Turacoz Healthcare Solutions aims to spread awareness about the role of patient advocacy groups in the rare disease research.