Product Registration

Getting marketing authorisation for medicinal products in more than one Member State in the EU is done by using one of three procedures:

“Centralised Procedure” - Regulation (EC) No 726/2004

“Mutual Recognition Procedure” and

“Decentralised Procedure” - Directive 2001/83/EC.

As well as these, national authorisations still allow products to be marketed in individual countries in the EU. Products could be authorised separately in several Member States by a number of national authorisations, alternatively one of these authorisations could be used to apply for authorization using the Mutual Recognition Procedure. Where products have national authorisation, the regulatory agency of the country concerned has to monitor and assess the safety of any products that have national authorisation.

Centralised Procedure

The EMEA administers the centralized procedure, where a single application, if approved, grants marketing authorisation for all the countries in the European Union (and the European Economic Area, that’s the EU countries plus Iceland, Norway and Liechtenstein). The European Commission becomes the responsible authority for products which come to market through the centralised procedure. This procedure is available to all new or innovative pharmaceuticals and is the only way to authorise biotechnology medicines. Where products contain new substances for treating serious diseases, they would use the centralised procedure.

The regulatory agency of one Member State is then appointed as the Rapporteur and they will then carry out initial assessments of the application for Marketing Authorisation; a second agency is appointed as Co-Rapporteur. These countries will then be responsible for leading the monitoring and assessment of safety of the product when it is subsequently marketed.

Mutual Recognition Procedure

In the Mutual Recognition Procedure the marketing authorisation of one member State is recognised and copied by the other member states. In this procedure, the ‘Reference Member State’, is “mutually recognised” by other ‘Concerned Member States’. Once the application for mutual recognition has gone in, there is a 90 day assessment period. After the assessment period the Member States grant a marketing authorisation with an identical summary of product characteristics to the one in the Reference Member State as long as they accept the original assessment of the product. If a Member State raises objections and does not recognise the original marketing authorisation then the matter may be referred to the EMEA for discussion among the parties: if this fails, binding arbitration is imposed.

Decentralised Procedure

The decentralised procedure can apply where there is no authorisation yet in any of the Member States. The same dossier is submitted to all Member States where a marketing authorisation is needed. The applicant selects a Reference Member State and prepares a preliminary assessment report within 120 days and sends it to the other states, the Concerned Member States. They then approve the assessment or the application will continue into a facilitation or, if this fails, a binding arbitration procedure applies.

Laws and guidelines

Laws

In the EU there are EU laws which are directives and regulations, and national laws. Once an EU regulation comes into effect it is in force in all the Member States of the European Union. However EU directives are different, once an EU directive comes into force it must first be enacted in national law in each EU Member State within a specified time-frame. As well as the national laws that put EU directives into action, there may also be national laws governing pharmacovigilance practice.

The principal EU laws concerning pharmacovigilance are:

Directive 2001/83, amended by Directive 2004/27. This concerns all medicinal products, although for pharmacovigilance it is most relevant to products authorised by the national, mutual recognition and decentralised procedures. The Member States are the licensing authorities in these procedures.

Regulation 726/2004. This concerns centrally authorised products. The European Commission is the licensing authority for these products.

Directive 2001/20. This is the Clinical Trials Directive and includes extensive coverage of pharmacovigilance for interventional clinical trials pre- and post-authorisation.

Guidelines

A word to the wise here. The guidelines tends to be suggestions or recommended methods. When it comes to EU pharmacovigilance law the guidelines are considered to be compulsory as far as pharmaceutical companies are concerned.

The European Commission guidelines provide detail and interpretation as to how the directives and regulations should be followed.The guidelines are also aimed at regulatory authorities and provide detailed requirements for the way that they must carry out pharmacovigilance as well. The guidelines are:

Volume 9A of the Rules Governing Medicinal Products in the European Community - for post-authorisation pharmacovigilance

Volume 10 of the Rules Governing Medicinal Products in the European Community. This applies to clinical trials pre- and post-authorisation and incorporates the guideline Detailed guidance on the collection, verification and presentation of adverse reaction reports arising from clinical trials on medicinal products for human use

As well as these laws and regulatory guidelines there are also various voluntary guidelines, generated for the most part by two organizations:

The Council for International Organizations of Medical Sciences (CIOMS)

The International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals (ICH).

CIOMS is a body set up under the World Health Organization and UNESCO. It has developed a series of guidelines on pharmacovigilance, drawn up by a committee of volunteers from Industry, regulatory authorities, WHO and others. The main guidelines concern the international reporting form (CIOMS I); periodic safety update reports (CIOMS II); core data sheets (CIOMS III); benefit-risk assessments (CIOMS IV); practical issues in pharmacovigilance (CIOMS V); clinical trial safety data (CIOMS VI); and development safety update reports (CIOMS VII).

Whilst CIOMS guidelines are very influential they are not “official” regulatory guidelines, they have no legal force and are generally there just to provide a consensus on good practices and new methodologies.

ICH consists of representatives of the regulatory authorities from the EU, Japan and US, with representatives of the corresponding industry regional organizations and Health Canada and WHO as observers. ICH establishes guidelines applicable to the EU, US and Japan through a series of expert working groups. There is a stepwise development of the guidelines. At Step 4, there is consensus internationally and at Step 5, an agreement by the regulators that they will introduce the guidelines into legislation, although there may be some divergence when these are actually put into effect in the different regions.

The three areas covered by ICH guidelines are Efficacy, Safety and Multidisciplinary. Paradoxically, the “Efficacy” guidelines include clinical (human) safety, whereas the “Safety” guidelines concern only pre-clinical (animal toxicology) safety.

The main guidelines concerning pharmacovigilance are:

E1: populations to be studied for safety and efficacy

E2A: reporting on safety in clinical trials

E2B: electronic reporting of adverse events

E2C: periodic safety update reports

E2D: reporting on safety post-marketing

E2E: pharmacovigilance planning

E2F: development safety update reports

M1: Medical Dictionary for Regulatory Activities

M4: the Common Technical Document (i.e. the international registration dossier)

Senior citizens purchase 35-40% of all prescribed and over-the-counter (OTC) drugs. Seniors between the ages of 65-84 take from 14-to-18 prescriptions annually. Up to 25% of these medications are considered unnecessary or inaccurate.

The Internet offers numerous articles and other information on how senior citizens can protect themselves from over-medication and other unnecessary treatments. Some of these articles are written by physicians who realize that medical drugs are not the answer to all health conditions. Additionally, a recent midwestern newspaper article points out that less than half of our medical care is supported by adequate scientific evidence, according to the experts. These kind of articles also offer recommendations for protection from the harmful side effects of too much medication.

Recommendations

1. Good insurance pays. Although health insurance is a good thing to have nowadays, do keep in mind that your insurance and drug plans could be prevailed upon for medical business reasons. If you already have medicare and other health insurance, your health condition could inadvertently be targeted for more treatments than really necessary.

2. Common sense. Listen to your best instincts about the treatments you might or might not need. Do not passively accept medication without knowing its exact health goal and purpose first. Ask questions about your prescription and why you need it for your specific condition Make sure this treatment makes sense to you.

Although senior citizens account for only 13% of the population, they purchase up to 40% of all medications. Therefore, document any side effects from your prescriptions, and report them to your doctor, e.g., headache, cough, drowsiness, dizziness, pain, itching, gas, upset stomach, or constipation. Your doctor can change these medications if they cause you discomfort.

3. Take someone with you to an appointment. Take a friend or family member with you when you see your doctor. This person will add to your advocacy by giving you emotional support, and by helping you thwart questionable prescriptions or treatments. Three heads are better than one. Also, remember that 77% of the seniors between the ages of 65-70 have at least one chronic illness. Thus, you could really need one or two prescriptions of some kind.

Yet, other prescriptions are questionable. For example, if you have a desirable cholesterol level lower than 200-mg/dL, and your doctor prescribes a statin drug to enhance your cholesterol level, you’ll need to question that recommendation to find out exactly why you need it for your apparent condition. Will it affect your other bodily systems in some way In another reported situation, a study at a northwestern state university found that some doctors were prescribing powerful anti-psychotic drugs to patients for mild depression, anxiety, and insomnia. These drugs are approved only for serious mental and emotional disorders. Otherwise, the effects from these drugs can be harmful.

Still other adverse medical effects can be somewhat innocent. In one case, a senior started taking two common OTC pills daily to help reduce hip pain. However, these pills thinned that person’s blood, which caused his or her small colon fissures to bleed. After the resulting blood showed up in the stool, this senior was much relieved to find out it was not caused by cancer.

4. Learn about your medical condition. If you have a computer available, search the Internet for reliable information about your condition, and how to treat it. If not, try a public or medical library to find out as much about it as you can. This kind of knowledge is defensive power in favor of your continued good health.

5. Keep and carry your own set of records. Carry your basic health history and information with you, in writing. List your chronic conditions, medications, allergies, blood type as well as your doctor’s name and phone number. Also keep a copy of these life-saving records in the open at your residence in case of an emergency, or in case you become unconscious and cannot provide this information verbally. Additionally, if possible, add copies of your laboratory test results to these records. Your life could depend on them.

6. Report suspected abuse or fraud. Medicare fraud costs tax payers multiple millions of dollars, and causes health insurance premiums to rise sharply. Learn how and where to report suspected abuse or fraud after carefully studying the suspect situation beforehand. Such abuse can be reported to a senior-medicare patrol in your area or state if they exist. These offices or patrols can sometimes be found at the government agencies on aging. For starters, see the links below.

The chiropractics profession has been around a long time and over the years dozens of different spinal manipulation methods have developed. Two of the most commonly used techniques are the Gonstead Technique and the Activator method. Which one is better for you? The following information may help you decide.

The Gonstead Technique

This technique was started by Dr. Clarence S. Gonstead of Wisconsin when he became a chiropractor in 1923. His idea of chiropractics references all body misalignments to the pelvic girdle, the body’s foundation according to the Gonstead theory.

Just like a building’s foundation needs to be level and firm to support the top of the building, the body’s foundation of the pelvic bones and the lower back bones needs to be level and in balance for the rest of the body to be secure and functioning well.

If these base bones become out of place at all through accidents or just abnormal movements, the whole body can be thrown out of whack. When the body is unable to naturally correct these misalignments, chiropractics is the key to setting things straight again.

Those using or following this concept will look carefully for misalignments in the upper back, but especially in the lower back near the pelvic bones. Manual techniques are often accompanied by spinal X-rays to get a complete understanding of the spine’s shape.

The theory then is once the exact problem vertebra is located, that problem area and nothing else should be adjusted back into place. Everything else will naturally fall into alignment when the root problem is fixed.

The Activator Method

This technique was created by Arlan Fuhr in the early 1960s with the introduction of his spring-load tool called the activator. The tool is used to replace manual manipulation of the spine and is often less jolting on the patient.

This is because the activator is used to pop misaligned vertebrae or joints back into place individually. In this procedure, the chiropractor has the patient lay flat, face down on a table while the doctor compares the length of the patient’s legs. If one leg appears shorter than the other, the chiropractor will press on individual vertebrae on the back to see if that makes a difference in the length of the leg.

That vertebra is then adjusted with a special tool and the doctor repeats this process until all necessary vertebrae have been realigned.

This is a very popular treatment in the United States today. A National Board of Chiropractic Examiners survey from 2003 found that almost 70 percent of American chiropractors employed the activator procedure in their practices. And this technique is taught is most of the chiropractics schools around the country today.

Both these procedures have many ardent followers among chiropractors and patients. Both have plenty of people who love each style and claim it works the best. You may need to try each method for yourself before you can determine which the best solution for your back troubles is.