Study: Changes in Pill Shape, Color May Lead to Lapses
In the latest study published on Monday, July 14 by Annals of Internal Medicine, research suggests that changes in a given medication’s color or shape may prompt patients to discontinue much-needed medicine after a heart attack.
As generic drugs continue to see an increase in consumption compared to their high-priced original counterparts, their variation in appearance may be causing confusion amongst patients, ultimately leading some to discontinue their use.
“Patients need to be on guard about pill appearance changes, particularly since it’s hard as a patient to know what’s going on when the blue pill you’re used to taking every morning suddenly is now yellow,” said lead author of the study Dr. Aaron S. Kesselheim, from Brigham and Women’s Hospital in Boston.
The authors of the study urge the Food and Drug Administration (FDA) to rethink their hands-off policy when it comes to regulating the appearance of generic medications.
The FDA does not require a consistent appearance for generic drugs that are otherwise clinically interchangeable – however, it must have the same active ingredient as the original and be delivered the same way – leaving room for aesthetic freedom of choice by the manufacturer.
Drug manufacturers who make generic pills negotiate deals with pharmacies, mail-order pharmacy benefit managers and hospital formularies with one thought in mind: price. The best price determines which pill (from the corresponding manufacturer) the patient will receive when the monthly refill comes around. A mail-order pharmacy may distribute a manufacturer’s drug one month, but then change manufacturers the following month resulting in the distribution of the same drug with a different appearance.
A loss of confidence in safety or effectiveness of the pill they are taking results in patients steering away from their medication, the authors summarized.
According to the U.S. Centers for Disease Control and Prevention, 20 to 30 percent of prescriptions are never filled, while 50 percent are not continued as prescribed.
Researchers studied the pill-taking habits of over 10,000 patients from around the world who were discharged after hospitalization due to a heart attack between 2006 and 2011. In the first year after an event such as a heart attack, it is critical that patients take certain medications to avoid complications and stay on the road to recovery.
But the study found that when patients noted a change in the appearance of their generic pills when going for a refill (29 percent), the odds that they would stop taking the drug increased by 34 percent for a change in pill color and 66 percent for a change in pill shape.
Changing pill appearance is not the most important factor contributing to medication non-adherence, but it is a new one to consider, said Kesselheim.
In addition to public policy actions, the authors said doctors should proactively inform patients about potential changes in pill colors and shapes, and reassure them that the medicines should work identically despite differing appearances.
“The more physicians and pharmacists can do to prepare patients that this might happen, I think the easier the transition will be,” Kesselheim said.
Medical device companies: how to prepare for Brexit
Over the last decade, medical device businesses have been no strangers to regulatory changes and new compliance requirements. Companies with devices in the EU market have been working hard to achieve conformity with the requirements of the EU Medical Device Regulation 2017/745 (MDR) and In Vitro Diagnostic Regulation 2017/746 (IVDR), but the UK’s exit from the EU, effective as of 1st January 2021, demands yet another change: to comply with the new UK regulatory regime.
The Medicines and Medical Devices Act passed into law on 11 February 2021 does just that; it enables the UK to build its own regulatory system, although when this new framework will be fully in place is not yet known.
The transition to the UK’s new regulatory regime officially began on the 1st of January 2021, and with it a series of deadlines and phases that medical device manufacturers exporting to GB and Northern Ireland would do well to take close notice of. During the transition period, the UK Medical Devices Regulations (UK MDR) 2002, not to be confused with the EU MDR, will continue to apply in England, Scotland and Wales, whilst CE marked medical devices will still be accepted up to 30th June 2023.
The conformity assessment processes defined in the UK MDR 2002 (as amended) will require that medical devices carry the UKCA mark for entry in the GB market or the UKNI mark for entry in Northern Ireland (where the devices are not CE marked for the EU). In Northern Ireland, where the rules for placing a device on the market differ, the EU MDR and IVDR will apply in 2021 and 2022 respectively, in line with the EU’s implementation timeline.
This easing-in period of transition is valuable time that should be used productively by manufacturers to ensure that they get up to speed, keep up with relevant updates and prepare strategies and product portfolio for the next phase. To do this, businesses should make sure they consider the following areas as they assess their strategy for UK market access:
Potential Overlap with EU MDR and IVDR
Medical device manufacturers have been working to implement measures to ensure they comply with EU MDR and IVDR for quite some time. The experience, processes and objective evidence that they have gathered in these efforts are certain to be of use when applying for UKCA marking.
Product portfolios and new product pipelines should be evaluated against both overall compliance risk and commercial and strategic value. By identifying the regulatory compliance status for each product for the UK market and the efforts required to maintain that compliance, manufacturers can plan to use the grace period up to June 2023 to complete their activities. These plans should also be evaluated in consideration of the commercial importance of the individual products to help prioritise the workload. This may well result in the decision to discontinue certain products in the UK or to introduce new products on the UK market ahead of other markets.
Engage with Approved Bodies
This activity cannot take place too soon; as of the 1st of January 2021, UK organisations that were acting as EU Notified Bodies have become Approved Bodies in the UK, while EU Notified Bodies are no longer able to provide conformity assessments under the UK regulations. As there are currently only three UK Approved Bodies offering this service, there is a very real risk that latecomers will struggle to find a UK Approved Body to carry out the conformity assessment required to attain their UKCA mark in time.
Just as EU Notified Bodies are no longer relevant to pursuing UK certifications, UK-based Authorised Representatives are no longer valid when CE marking against the MDR or IVDR. Manufacturers using UK-based EU Authorised Representatives must switch to an EU-based Authorised Representative.
For the UK market, the role of the EU Authorised Representative is also no longer applicable. Non-UK manufacturers must have a UK-based Responsible Person (UKRP), which is equivalent to the EU Authorised Representative in terms of roles and responsibilities. Only one UKRP may be appointed, unlike EU Authorised Representatives, and they must have a registered place of business in the UK in order to register with the MHRA. Approved Bodies may be able to provide details of organisations acting as UKRPs and once this role has been assigned it will be critical for manufacturers to determine exact procedures for managing documentation and that clear communication channels are established.
Labelling and Import/Export
New UK regulations require that medical devices bear a UKCA mark in addition to the name and address of the UKRP for non-UK based manufacturers. Manufacturers who use the same products/packs for the EU and UK markets will need to consider the impact of adding more content to their labels in terms of usability for the supply chain and end-users.
While CE marking and certificates will continue to be recognised by the UK until June 2023, import/export administration is likely to change and become more burdensome. Manufacturers using separate products for GB (UKCA) and the EU and Northern Ireland (CE marked) will need to plan for how to ensure that the CE marked product is not shipped to GB post June 2023. Ensuring that processes and resources are in place to deal with developing situations will help manufacturers hit the ground running.
Many businesses will find that clinical investigations are carried out across multiple sites, some of which are outside the UK. In these instances, manufacturers will do well to have a plan for implementation and management of investigations, in compliance with local requirements. It is likely that the MHRA will also continue to update their requirements for clinical trials in the UK.
Data Protection and Standards
New tensions are emerging between the EU and the UK concerning UK data protection rules and the EU’s General Data Protection Regulation (GDPR), suggesting that maintaining ‘equivalency’ may involve a number of different phases.
Compliance with applicable standards also requires close attention; the list of designated standards for medical devices issued by the UK’s Department for Health and Social Care is based on the list of harmonised standards published in the Official Journal of the EU, which in turn are harmonised to the MDD, AIMDD and IVDD. More recently published standards, however, have not been harmonised to the latter European directives and are thus not in the UK’s designated list, despite being considered state of the art. It would be prudent for manufacturers to monitor the state-of-the-art standards and apply where applicable, rather than rely on superseded and outdated standards.
As the UK moves into a new regulatory regime, medical device manufacturers who have already invested time and resources to comply with EU MDR and IVDR can use this to attain their UKCA mark. However, a dynamic compliance environment combined with the new onus relating to export policies means that close attention needs to be paid on numerous fronts. Keeping pace with this changing environment will ensure that manufacturers face the future with confidence and do not lose important space on their markets.